Massachusetts Eye and Ear Enters Licensing Agreement with Biogen to Develop Treatment for Inherited Retinal Disorder – Newswise

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Newswise Massachusetts Eye and Ear, a member hospital of Mass General Brigham, is entering into an exclusive licensing agreement with Biogen to develop a potential treatment for inherited retinal degeneration due to mutations in the PRPF31 gene, which are among the most common causes for autosomal dominant retinitis pigmentosa.

Inherited retinal degenerations (IRDs), such as retinitis pigmentosa, are a group of blinding eye diseases caused by mutations in over 270 different genes. Mutations in the PRPF31 gene are the second most common cause of dominant IRD and lead to defects in the function of the retinal pigment epithelial (RPE) cells and photoreceptors of the retina. Previous lab-based research performed by members of the Ocular Genomics Institute at Harvard Ophthalmology, led by Eric A. Pierce, MD, PhD, demonstrated that adeno-associated virus (AAV)-mediated gene augmentation therapy for PRPF31 can restore normal function to PRPF31 mutant RPE cells.

Biogen (Nasdaq: BIIB), a biopharmaceutical company that discovers, develops, and delivers worldwide innovative therapies for people living with serious neurological and neurodegenerative diseases as well as related therapeutic adjacencies, will build upon this prior work, and conduct the studies needed for clinical development of PRPF31 gene therapy. This includes the pre-clinical studies needed to support progression to clinical trials of PRPF31 gene therapy. As part of the agreement, Biogen will receive an exclusive license to develop the product worldwide and will be responsible for all U.S. Food and Drug-Administration (FDA) required investigational new drug (IND) enabling studies, clinical development and commercialization.

The treatment of IRDs with highly effective AAV-based gene therapies is core to Biogens ophthalmology strategy, said Chris Henderson, Head of Research, Biogen. This agreement underscores our commitment to that strategy and builds off of our acquisition of Nightstar Therapeutics in 2019 and our active clinical trials of gene therapies for different genetic forms of IRD. We are excited to work with Massachusetts Eye and Ear and look forward to applying our preclinical and clinical experience to their leading PRPF31 program.

We are thrilled to work with Biogen, who will bring to this effort its deep experience with the clinical development process, as we work toward our goal of developing a gene therapy for people with PRPF31-related eye disease, added Dr. Pierce, who is the William F. Chatlos Professor of Ophthalmology at Harvard Medical School. My ultimate hope for patients with inherited retinal disorders due to mutations in PRPF31 is that a gene therapy will preserve and potentially restore some of their vision.

About the Ocular Genomics Institute

The Ocular Genomics Institute at Harvard Ophthalmology aims to translate genomic medicine into precision ophthalmic care for patients with inherited eye disorders. It is home to one of the leading centers for early-phase clinical trials of therapies for inherited retinal degenerations, with seven gene-based and one stem cell trial currently in progress. The group works in conjunction with other departments throughout Harvard Medical School and Mass. Eye and Ear, including the Bioinformatics Center and Grousbeck Gene Therapy Center.

Dr. Pierces lab, established in 2011, is dedicated to research in an effort to improve the understanding of the molecular bases of IRDs so that rational therapies can be developed for these diseases.

In 2018, Mass. Eye and Ear surgeons performed the first post-FDA approval gene therapy for patients with a form of inherited retinal blindness caused by mutations in the gene RPE65 by injecting an AAV-based drug treatment into a patients eye, which restored vision in a 13-year-old boy. This therapy, called Luxturna, is now being used to treat patients with RPE65-associated retinal degeneration around the world.

One of the exciting aspects of our collaboration with Biogen is that mutations in the PRPF31 gene affect approximately 10 to 20 times more people than mutations in the RPE65 gene, said Dr. Pierce. Success with PRPF31 gene therapy could provide visual benefit to more patients, which is our ultimate goal.

Mass. Eye and Ear was one of the first centers to offer life-changing gene therapies to patients with inherited retinal disease, and we are thrilled with this new opportunity to develop a translational retinal therapy that could help even more patients, said Joan W. Miller, MD, Chief of Ophthalmology at Mass. Eye and Ear, Massachusetts General Hospital, and Brigham and Womens Hospital, and Chair of Ophthalmology and the David Glendenning Cogan Professor of Ophthalmology at Harvard Medical School.

According to Chris Coburn, Chief Innovation Officer, Mass General Brigham, the collaboration with Biogen illustrates the importance of academia and industry teaming to solve problems for patients worldwide. We are eager to see this progress reach patients who are challenged by blinding, degenerative eye disease, said Coburn. We look forward to working with Biogen to advance this break-through innovation.

Patients with an inherited retinal disease require genetic testing prior to being considered for any gene therapy treatment.

About Massachusetts Eye and Ear

Massachusetts Eye and Ear, founded in 1824, is an international center for treatment and research and a teaching hospital of Harvard Medical School. A member of Mass General Brigham, Mass. Eye and Ear specializes in ophthalmology (eye care) and otolaryngologyhead and neck surgery (ear, nose and throat care). Mass. Eye and Ear clinicians provide care ranging from the routine to the very complex. Also home to the world's largest community of hearing and vision researchers, Mass. Eye and Ear scientists are driven by a mission to discover the basic biology underlying conditions affecting the eyes, ears, nose, throat, head and neck and to develop new treatments and cures. In the 20192020 Best Hospitals Survey,U.S. News & World Reportranked Mass. Eye and Ear #4 in the nation for eye care and #2 for ear, nose and throat care.For more information about life-changing care and research at Mass. Eye and Ear, visit our blog,Focus, and follow us onInstagram,TwitterandFacebook.

About Harvard Medical School Department of Ophthalmology

The Harvard Medical SchoolDepartment of Ophthalmologyis one of the leading and largest academic departments of ophthalmology in the nation. Composed of nine affiliates (Massachusetts Eye and Ear, which is home to Schepens Eye Research Institute; Massachusetts General Hospital; Brigham and Womens Hospital; Boston Childrens Hospital; Beth Israel Deaconess Medical Center; Joslin Diabetes Center/Beetham Eye Institute; Veterans Affairs Boston Healthcare System; Veterans Affairs Maine Healthcare System; and Cambridge Health Alliance) and several international partners, the department draws upon the resources of a global team to pursue a singular goaleradicate blinding diseases so that all children born today will see throughout their lifetimes. Formally established in 1871, the department is committed to its three-fold mission of providing premier clinical care, conducting transformational research, and providing world-class training for tomorrows leaders in ophthalmology.

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Massachusetts Eye and Ear Enters Licensing Agreement with Biogen to Develop Treatment for Inherited Retinal Disorder - Newswise

Pools in the Mexican desert are a window into Earth’s early life – Science Magazine

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Azure pools rich in magnesium and calcium carbonate but low in phosphorus provide an ideal habitat for ancient bacterial reefs at Cuatro Cinegas, in theChihuahuan Desert of Mexico.

By Rodrigo Prez Ortega Jun. 30, 2020 , 3:40 PM

Valeria Souza Saldvar never planned to devote her life to a remote and ancient oasis more than 1000 kilometers north of her laboratory in Mexico City. But a call in early 1999 changed that.

Its one of the best cold calls Ive ever made, says James Elser, a limnologist at the University of Montana. He had picked up the phone to invite Souza Saldvar to join a NASA-funded astrobiology project in Cuatro Cinegasa butterfly-shaped basin with colorful pools, or pozas, in the middle of Mexicos Chihuahuan Desert.

Neither Souza Saldvar, a microbial ecologist at the National Autonomous University of Mexico, University City, nor her ecologist husband and research partner Luis Eguiarte Fruns, also at UNAM, had ever visited Cuatro Cinegas. That first trip convinced them to completely change their research plans. Looking at those mountains and the water, I fell in love, Souza Saldvar says.

The landscapemore than 300 turquoise-blue pozas scattered across 800 square kilometers, among marshes and majestic mountainswasnt the only draw. The waters, whose chemistry resembled that of Earths ancient seas, teemed with microbes; unusual bacterial mats and formations called stromatolites carpeted the shallows. When Souza Saldvar first cultured the organisms from the pozas, The amount of microbes was enormous, as was the diversity of colors and colony sizes, she recalls. For her, this remote microbial hot spot was an irresistible mystery.

Since then, work by Souza Saldvar, Eguiarte Fruns, and a widening circle of collaborators in Mexico and the United States has shown that Cuatro Cinegaswhich means four marshes in Spanishis one of the most biodiverse places on the planet. Theres nowhere that has so much ancient diversity of microorganisms, says Michael Travisano, an evolutionary ecologist at University of Minnesota, Twin Cities, who has collaborated with the Mexican researchers since 2001. Among the most recent additions to that menagerie are hundreds of species of archaea, the ancient microbes that may have given rise to eukaryotesorganisms with complex, nucleated cells.

At the Pozas Azules ranch in Cuatro Cinegas, about 100spring-fed pools dapple the desert. Each has a unique microbial and mineral composition.

The diversity includes strains with unusual adaptations, such as the ability to build their lipid membranes with sulfur instead of the usual phosphorus, which is scarce in the waters of thepozas. It includes potential sources of new compounds for medicine and agriculture. And it poses a question that has occupied Souza Saldvar and Eguiarte Fruns for the past 20 years: How did this Noahs Ark of ancient microbes arise? Its a dream for every biologist to know the origin of diversification, Souza Saldvar says.

But her dream might be short-lived. Since the 1970s, farmers have intensively drained water from thepozasand rivers to irrigate nearby fields of alfalfa, grown for cattle fodder, gradually drying the improbable oasis. Souza Saldvar has galvanized a conservation effort that has slowed the drainage; in the coming weeks, a canal that removes 100 million cubic meters of Cuatro Cinegass water annually is scheduled to close. In the meantime, the researchers have been trying to describe as much as they can, as fast as they can, before their belovedpozasdry up and the precious microscopic life that has survived undisturbed for millions of years dies off.

Cuatro Cinegasservedas a stopping point for hunter-gatherers for thousands of years. To date, 50 archaeological sites with cave paintingssome dating to 2275 B.C.E.have been found in mountain cavesaround the basin. Much later, the region made a mark on history when Venustiano Carranza, born in a village at the basins margin, became a leader of the Mexican Revolution and president of Mexico from 1917 to 1920. Nowadays, the village is called Cuatro Cinegas de Carranza after him.

But in the 1960s, Cuatro Cinegas started to become famous for its biodiversity, as biologists began to describe new species of snails, fish, turtles, and plants found in the pools and marshesand often nowhere else.

Wendell Minck Minckley, a renowned ichthyologist at Arizona State University (ASU), Tempe, was first lured to Cuatro Cinegas after learning thatthe worlds only aquatic box turtle(Terrapene coahuila) lived there. Over the years, Minckley made frequent trips to thepozas, describing their snails and fish (Herichthys minckleyi, a cichlid, bears his name) while making connections with the local people.

In the Cuatro Cinegas Basin, ringed with mountains and desert, an aquifer feeds hundreds of pools and marshes. But canals tapping water for agriculture threaten the wetlands and the biodiversity they host.

(MAP) N. DESAI/SCIENCE; (DATA) E. MAMER AND T. NEWTON/NEW MEXICO BUREAU OF GEOLOGY AND MINERAL RESOURCES; VALERIA SOUZA SALDVAR; NATIONAL COMMISSION OF NATURAL PROTECTED AREAS MEXICO

Minckley also noticed peculiar, rocky structures in the pools. They were stromatolites, biological structures normally found as fossils dating back as much as 3.5 billion years. Colonies of photosynthesizing bacteria, which boosted early Earths oxygen, created the layered formations by depositing carbonates and trapping sediment in ancient, shallow seas. But these stromatolites were alive. Also found in other extreme environments such as Australias warm, salty Shark Bay, living stromatolites are sort of a window into early Earth, Elser says. Thepozasalso nurture bacterial mats, a soft form of stromatolites normally found deep in the ocean.

As early as the 1970s, Minckley realized the pools and their diversity were under threat: Local farmers were carving canals to tap their water. Thanks in part to his lobbying, the Mexican government in 1994 designated an 85,000-hectare protected area. But the drainage continued. Minckley knew that Cuatro Cinegas was going to die, Souza Saldvar says. He thought NASA might be its salvation.

In 1998, NASA established its Astrobiology Institute, a network of researchers studying life in extreme environments that might resemble conditions on other planets. Minckley saw an ideal astrobiology study site in the waters of thepozas, with their seemingly inhospitable chemistry and living stromatolites. But he was no expert on extreme environments, so he enlisted Elser, who specializes in how water chemistry affects ecosystems and also works at ASU. After they submitted a 1998 proposal to fund the project, however, NASA said they should add experts on microbiology and evolutionand those experts had to be Mexican to help secure permits to obtain samples. Based on colleagues suggestions, Elser called Souza Saldvar and Eguiarte Fruns, newly minted professors at UNAM. They joined, and NASAapproved the 3-year project.

Stromatolites, reeflike colonies of carbonate-secreting cyanobacteria, abounded in Precambrian seasand thrive at Cuatro Cinegas.

With two children in tow, the couple met Minckley and Elser at Cuatro Cinegas. Next to the turquoise-blue waters of La Becerrapoza, Minckley told them he believed the ecosystem was a glimpse of deep time. Do you see these miniature snails in my hand? Souza Saldvar recalls him saying. I just scooped them from the springhead, but their direct ancestors were eating sulfur bacteria in hydrothermal vents 220 million years ago in the bottom of the ancient Pacific.

Based on the water chemistrylow in phosphorus, iron, and nitrogenand the presence of living stromatolites, Minckley believed Cuatro Cinegas re-created the marine conditions found worldwide millions of years ago. He challenged the two researchers to explore its mysteriesand to protect itspozas. Only you, as Mexicans, can save them from the extinction caused by humans, Souza Saldvar recalls him saying.

Minckleydied2 years later, in 2001.

To inventory the full diversityof microbes at Cuatro Cinegas and trace their relationships, Souza Saldvar needed to study their DNA. To do so, scientists normally take microbial samples from a site and grow them in a lab. But many bacteria and archaea are difficult to culture, and only a few groups at the time had successfully analyzed DNA isolated directly from the environment. High magnesium levels in the water and slime from the microbes made isolating DNA from thepozasespecially difficult.

But Souza Saldvar and her students Ana Escalante and Laura Espinosa Asuar made a start. In 2006, they reported in theProceedings of the National Academy of Sciencesthat they had found 38 distinct groups of microbesfour times as many as in a typical salt marshcorresponding to 10 major lineages of bacteria and one of archaea. Half the bacterial groupswere most closely related to marine microbes. Almost 10% of the groups resembled ones that live on hydrothermal ventsfissures deep in the ocean where microbes thrive despite extreme heat and mineral concentrations.

As Minckley had suspected, Cuatro Cinegas had somehow preserved ancient marine life forms deep in the desert, more than 500 kilometers from the Gulf of Mexico, at a site where the last seas retreated some 20 million years ago.

Valeria Souza Saldvar and Luis Eguiarte Fruns (top) have spent 20 years studying biodiversity at Cuatro Cinegas, where they have found thousands of new species in living structures like a bacterial mat (bottom).

The deep time aspect [of Cuatro Cinegas] is very surprising, Travisano says. It is a true lost world, preserved by the hostile water chemistry, he and the Mexican team argued in a 2018 paper ineLife. Millions of years ago, they proposed, ancient marine ancestors found their way to the place,adapted to the extreme environment, and didnt change much.

Thepozasthemselves are not particularly ancient. The springs that nurture them are fed by deep aquifers in Sierra San Marcos y Pinos, filled with water accumulated during the last ice ages, Eguiarte Fruns says. Now, the water seeps to the surface because of an active fault beneath the basin. It rises through ancient marine sediments, picking up its unusual chemistry along the way. Somehow, the ancient microbespersisted and diversifiedin a succession of springs that must have appeared and vanished throughout geologic time. As in an ancient clock, Souza Saldvar says, all the original mechanisms are still working together to sustain unusual life.

To Frederick Cohan, a microbial ecologist at Wesleyan University who is not part of the Cuatro Cinegas project, the fact that many of the microbes are related to marine species and not species found inland is compelling. I think its saying those organisms are anciently there.

When the researcherslooked at the stromatolites, theyfound even more diversity. Samples from one site, Pozas Azules II, yielded more than 58,000 distinct microbial sequences, predominantly from bacterianot a direct count of species, but an indicator of biodiversity. In the Ro Mezquites, a stream that flows through the northern part of the basin and recharges several pools, they identified 30,000 sequences, mostly from cyanobacteria. More than 1000 sequences from Pozas Azules II appeared to be from archaea, the researchers reported inEnvironmental Microbiologyin 2009. The stromatolites also teemed with bacteria-infecting virusesstrains that wereunique to each pooland resembled marine viruses.

Studying the microbes hasnt been easy. There are thousands and thousands of new bacteria that we cant grow in culture, Souza Saldvar says. They could, however, identify some startling adaptations to the extreme conditions. In one bacterium found only in El Churince, a system of lagoons andpozason the western part of the basin, researchers sequenced the smallest genome ever found in its genus,Bacillus. The work, led by Gabriela Olmedo lvarez, a genetic engineer at Center for Research and Advanced Studies of the National Polytechnic Institute, Irapuato, also showed that the microbeB. coahuilensiscould synthesize membrane sulfolipids. This meant that, like some plants and cyanobacteria, it could use sulfur from the environmentinstead of phosphorusto form its cell membranes.

Shallow, mineral-rich pools and lagoons, with conditions like those in ancient oceans, are hot spots of microbial diversity. Floating mats at Cuatro Cinegas teem with the primordial microbes known as archaea, leading researchers to call them archaean domes.

(GRAPHIC) N. DESAI/SCIENCE; (DATA) GARCIA-MALDONADO ET AL., EXTREMOPHILES, DOI 10.1007/S00792-018-1047-2; CENTENO ET AL., MICOBIOLOY ECOLOGY, DOI: 10.1111/J.1574-6941.2012.01447

It likely stole these genes from a cyanobacterium, Olmedo lvarez says, enabling it to cope with scarce phosphorus, a condition thought to have prevailed in Earths earliest oceans. The microbes small genome may also have helped it thrive, as it required less phosphorus to build its DNA. Olmedo lvarez thinks the organism may offer a glimpse of the stratagems used by early microbes to adapt to their new environment.

Were just starting to understand the depth of diversity, says Olmedo lvarez, who found thatB. coahuilensisis itself starting tosplit into strainswith variations in phosphorus metabolism.

The low phosphorus conditions found in Cuatro Cinegas not only promoted local adaptations, but alsoaccelerated microbial diversification, Souza Saldvar and Elser argued in a perspective published in 2008 inNature Reviews Microbiology. Bacteria normally share bits of DNA with their neighbors in a process called horizontal gene transfer, which blurs the divisions between strains. But in Cuatro Cinegas, the microbeshungry for phosphorusessentially consume free DNA rather than incorporating it into their genomes. They will eat the DNA to get the phosphorus, Elser says.

Besides offering insights into evolution, Cuatro Cinegass microbial diversity may hold practical payoffs. Cuatro Cinegas is one of the richest places on the planet for genetic resources, Souza Saldvar says. For example, most modern antibiotics are derived from actinobacteria, which are abundant in thepozas. Susana De la Torre Zavala, a biotechnologist at the Autonomous University of Nuevo Len (UANL), University City, is searching for potential antibiotics in a library of 350 actinobacteria from the basin. Her team has also found that an extract from a microalga living in the poolsshows anticancer activity.

Agriculture, too, could benefit, Olmedo lvarez says. By 2050, the reservoirs of phosphorus that help sustain global harvests could become scarce, and the microbesability to concentrate the element from different sourcescould hold solutions. Were understanding Cuatro Cinegas, but were also understanding basic principles of ecological interactions that have an application in medicine and agriculture, she says.

As the scientific storyof Cuatro Cinegas unfolded, its fate has hung in the balance, with Souza Saldvar fighting a long series of battles over its water with local farmers and landowners, dairy companies, and politicians. Her weapons have been her rising scientific profile and a tireless outreach to the public, especially young people.

Souza Saldvar has drawn fireduring a 2013 microbiology congress, police had to protect her from protesting localsbut she has won a series of victories. In 2007, the daughter of the CEO of LALA, a giant dairy consortium with roots in the state of Coahuila, told her father she wouldnt speak to him because he was killing Cuatro Cinegas, Souza Saldvar says. The executive promptly scheduled a meeting with the scientist. You need to change your cows diet, Souza Saldvar says she told him, refusing to accept a courtesy yogurt he offered. Ill accept your yogurt when you do so. He promised not only to stop buying the regions alfalfa, but also to invest in environmental education projects for local children.

Two years later, she won an unusual ally, the powerful Mexican billionaire Carlos Slim. His foundation collaborated with the World Wildlife Fund (WWF) to buy the land surrounding El Churince in the western basin, and to provide researchers with a 5-year, 18 million Mexican peso ($1.4 million) grant to study Souza Saldvars favoritepoza. This allowed them to set up the infrastructure to perform long-term experiments. But it did not save the water.

Endemic fishes and turtles first drew scientists to Cuatro Cinegas, where they stumbled on its less visible microbial riches.

In 2010, Mexicos National Water Commission (CONAGUA) set out to replace the open, leaky canals, which lose 75% of the drained water, with less wasteful enclosed conduits. But the project was abandoned midwaymost likely because of corruptionand the old canals were never closed. As Cuatro Cinegas continued to dry up, the researchers raced to study El Churince, finding 5167 distinct species of bacteria and archaea in the last remaining pool. A close inspection of the genomes ofBacillusbacteria from one single square kilometer increased the known diversity of the group by more than 20%. By comparing DNA sequences, the team traced theBacillusdiversity to two ancient ancestors, one dating back 680 million years, the other 160 million years. Those dates coincide with the breakup of the supercontinents Rodinia and Pangaea, respectively, and the team thinks theoceans that formed during those convulsions carried the ancestral microbesto what is now the Cuatro Cinegas Basin, where they have persisted ever since.

Cohan says thats plausible.Bacillusfrom elsewhere fail to thrive in Cuatro Cinegas, most likely because they are outcompeted by the local microbes and cant adapt to the extreme conditions. And theBacillusspecies from Cuatro Cinegas are not found anywhere else in the world. Its just bizarre, Cohan says, but it makes thepozasso much more valuable and worth saving. Its kind of a paleontological microbial park.

In 2016, El Churince dried up just after the funding from the WWFCarlos Slim Foundation ended. The researchers felt devastated. Souza Saldvar says it was painful to see turtle shells lying on the now-barren soil. Its really sad, Olmedo lvarez says. Its gone.

On the eastern sideof the basin, things are looking brighter. In 2000, the conservation nongovernmental organization Pronatura Noreste acquired the Pozas Azules ranch: 2721 hectares hosting about 100pozas. Pronatura eventually gained rights to the water as well, enabling it to close canals draining thepozasin the ranch. Farmers are now encouraged to adopt water-sparing drip irrigation, and some are growing nopalan edible cactus popular in Mexican cuisinewhich requires much less water than alfalfa.

The researchers have focused their recent studies on Pozas Azules. In 2019, after an unusual spring rain, the team noticed alien-looking structures in the shallow waters of a site near Pozas Azules II: white microbial mats buoyed by gas. The gas appeared to be largely methane, and a genetic analysis showed the mats were teeming with archaea230 distinct species,they report in a preprint. That makes the spot the most diverse place of archaea that we know of, De la Torre Zavala says.

Now, the team hopes to analyze samples from the structures, which it calls archaean domes, in search of the elusive Asgard archaea, organisms previously found only in the deep ocean and thought tohold clues to the evolution of simple microbesinto complex eukaryotes. Although some in her team are skeptical, Souza Saldvar is convinced they will find them. Valerias usually right, De la Torre Zavala says.

Shaped and seeded with life by ancient seas, the Cuatro Cinegas Basin lies at the foot of the distant Sierra San Marcos. The white dunes bordering the basin are made of gypsum, a legacy of a Jurassic ocean.

Such prospects have added to Souza Saldvars determination to preserve Cuatro Cinegas, and she is enlisting young people for support. In every field trip since 2004, her team has spent time with students from the local high school, showing them how to use a microscope and take simple environmental measurements, and teaching them about sustainable agriculture. In 2011, with funding from the LALA Foundation and the WWFCarlos Slim Foundation, the scientists set up a college-level molecular biology lab at the school, which is now ranked among the best rural high schools in Mexico.

Hctor Arocha Garza is one of its graduates. Inspired by the secrets of Cuatro Cinegas, he pursued a Ph.D. in biotechnology at UANL with De la Torre Zavala, then returned to his hometown. My heart was in Cuatro Cinegas, he says. Now, hes leading the scientific branch of a privately fundedmegaproject called Cuatro Cinegas 2040that aims to build a science museum and make Cuatro Cinegas a scientific tourism destination, while supporting education and medical care for the villages young people.

The effort comes at a critical moment. More than 90% of the marshes are gone, and somepozasand lagoons are dry. But this year, CONAGUA committed toregulating water usageand closing illegal wells, and Pronatura Noreste will close the Saca Salada Canal, which drains the Ro Mezquites, as soon as the COVID-19 pandemic permits.

Those developments, and stories like Arocha Garzas, give Souza Saldvar hope for the future of Cuatro Cinegas. It has been a very complicated, long, and difficult process, she says. But now, she wrote in a recent book, There is a revolution occurring in this oasis: Science is the tool and kids are the drivers.

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Pools in the Mexican desert are a window into Earth's early life - Science Magazine

Research Roundup: COVID-19 Immunity and More – BioSpace

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Every week there are numerous scientific studies published. Heres a look at some of the more interesting ones.

Hamster Models of COVID-19 Show Protective Immunity

The jury is still out whether people who had COVID-19 can get it again, but animal studies are suggesting they cant. A study out of the University of Wisconsin-Madison in hamsters demonstrated that previous infection with SARS-CoV-2 provided protection against getting infected again. And experiments with convalescent serumusing the blood serum from previously infected patientslimited viral replication in the lungs. The research was published in the Proceedings of the National Academy of Sciences and in Science.

Hamsters are good models for human influenza and SARS-CoV, said Yoshihiro Kawaoka, professor of pathobiological sciences in the UW School of Veterinary Medicine and a virology professor at the University of Tokyo. This is why we decided to study them with COVID-19. We wanted to see if the disease course is similar to humans in these animals from beginning to end.

The study also evaluated infections at both low and high doses, finding that the virus could infect both the upper and lower respiratory tracts. But the key findings were the apparent immunity to reinfection.

The animals all possessed antibodies and did not get sick again, which suggests they developed protective immunity, said Pete Halfmann, a research professor in Kawaokas U.S. lab. But we still cant say how long this protection lasts.

Changes in Blood Vessels in the Eyes May Predict Alzheimers

A study led by researchers at Cedars-Sinai identified early molecular and cellular loss in blood vessels in the retina as well as an accumulation of amyloid-beta in Alzheimers patients. The amyloid-protein accumulation is a signature of Alzheimers, but the researchers mapped the vascular abnormalities in the retinal blood vessel walls and found that certain regions of the retina were more vulnerable. The study evaluated 62 postmortem eye tissues of 29 patients who had Alzheimers, 11 with mild cognitive impairment and 22 with normal cognition. In the Alzheimers patient, they found three abnormalities within tiny blood vessels in the retina: high death rates for pericytes; low levels of PDGFR; and an accumulation of amyloid-beta. The researchers believe this could lead to potentially noninvasive retinal imaging for diagnosing Alzheimers years before symptoms develop.

Inherited Mutation in Brazilians Increases Risk of Cancer

Researchers at St. Jude Children's Research Hospital and international colleagues found a variant in the tumor suppressor gene XAF1 that with a TP53-R337H mutation increases cancer risk. The TP53-R337H inherited variant in Brazilians was identified more than 20 years ago. It is rare in the general population, but common in 1 out of every 300 Brazilians. But the mutation itself did not explain the complete cancer risk. But it was a variant in the XAF1 gene in a subset of TP53-R337H mutation carriers that demonstrated a much greater risk of cancer. The research has implications for evaluating cancer risk in Brazilians and for public health evaluations.

Using Light to Treat Cancer

Investigators with Nagoya University are treating a rare form of malignant lung cancer with near-infrared irradiation and a cancer-targeting molecule. The disease is malignant pleural mesothelioma (MPM). It rarely metastasized but is usually diagnosed too late for good treatment options. The group tested the effectiveness of near-infrared photoimmunotherapy (NIR-PIT) along with an antibody linked to a photoabsorber (IR700). When near-infrared light is shone on the part of the body affected by cancer, the compound targets the cancer cell membranes, causing acute cell rupture and tumor death.

Early COVID-19 Infection Rate Possibly 80 Times Greater than Originally Reported

A new research study out of Penn State estimates that the number of early COVID-19 cases in the U.S. were more than 80 times higher and doubled almost twice as fast as originally reported. The research was published in the journal Science Translational Medicine. They focused on the Centers for Disease Control and Preventions influenza-like illnesses (ILI) surveillance data for a three-week period in March 2020. They believe that each states ILI reporting could not be attributed to the flu and exceeded seasonal baseline levels. They also found that the excess ILI almost perfectly matched the spread of COVID-19 around the country.

Our results suggest that the overwhelming effects of COVID-19 may have less to do with the virus lethality and more to do with how quickly it was able to spread through communities initially, said Justin Silverman, assistant professor in Penns College of Information Sciences and Technology and Department of Medicine. A lower fatality rate coupled with a higher prevalence of disease and rapid growth of regional epidemics provides an alternative explanation of the large number of deaths and overcrowding of hospitals we have seen in certain areas of the world.

A Soy Derivative Might Reduce Cognitive Impairment

In a study out of Kyushu University in mice, a protein fragment derived from soy reduced memory degradation in Alzheimers mouse models. The molecule is classified as a dipeptide and is the only one known to travel from a mouses stomach to its brain intact.

On top of the possibility of being broken down during digestion, peptides then face the challenge of crossing a highly selective barrier to get from the blood into the brain, said Toshiro Matsui, professor in the Faculty of Agriculture at Kyushu University and leader of the study published in npj Science of Food. While our previous studies were the first to identify a dipeptide able to make the journey, our new studies now show that it can actually affect memory in mice.

Working with colleagues at Fukuoka University, the scientists studied the effect of the dipeptide, named Tyr-Pro, by feeding it to mice for several days before and after dosing them with a chemical often used to simulate Alzheimers disease. They tested the mices short-term memory using a simple maze and found that the mice who ate the dipeptide over the past two weeks did better than those who did not, although both groups did not run the maze as well as mice without induced memory impairment. Long-term memory tests had similar results.

We still need studies to see if these benefits carry over to humans, but we hope that this is a step toward functional foods that could help prevent memory degradation or even improve our memories, Matsui said.

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Research Roundup: COVID-19 Immunity and More - BioSpace

Challenge trials aren’t the answer to a speedy Covid-19 vaccine – STAT

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More than 25,000 people have volunteered so far to be infected with the novel coronavirus through 1DaySooner, an online recruitment organization, as an aid in testing vaccine candidates to prevent Covid-19. These volunteers know that Covid-19 can cause suffering and even death yet they are stepping forward, willing to risk their lives, because some researchers and academics contend that such experiments in humans could accelerate vaccine development.

As a physician and a scientist who has cared for patients and who has been involved in the development of vaccines, I feel the urgency to get a vaccine approved for global use. And I have deep admiration for the courageous volunteers who are willing to put themselves in danger.

In this situation, however, their sacrifice cannot be justified. Volunteers need to be protected from both known and unknown risks. The effort to develop a vaccine should not be jeopardized by this well-intentioned but unnecessary experiment.

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In the context of an ongoing pandemic, the conventional pace of vaccine development frustrates the public, the government, public health experts, vaccine creators, regulators, and others. It is understandable that many are seeking ways to accelerate the demonstration of safety and efficacy of vaccine candidates. The mumps vaccine, considered the fastest vaccine ever developed, took scientists four years to go from collecting viral samples to securing FDA approval in 1967. A decade or longer is more typical. Everyone is hoping that inventing, testing, obtaining approval and producing a Covid-19 vaccine might be on track to set a new record.

The practice of deliberately infecting people with disease, termed human challenge trials, has a long history. It is embedded in the origin of the very first vaccine in 1796, when Edward Jenner, an English physician, purposely infected his gardeners 8-year-old son with cowpox after observing that people previously infected with cowpox, a relatively mild disease, seemed protected from smallpox, one of the deadliest scourges of the time.

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Now, in the midst of the coronavirus pandemic, human challenge studies are being considered again.

In the June 1 issue of the Journal of Infectious Diseases, Nir Eyal, Marc Lipsitch, and Peter G. Smith argue that this approach could accelerate the development and approval of a Covid-19 vaccine by many months. That may sound tempting, but human challenge studies with live virus are unlikely to save time. Moreover, there are ethical and practical reasons for not undertaking human challenge studies with this virus. These authors, like 1DaySooners volunteers, are well-intentioned but wrong.

Those in favor of human challenge trials propose enrolling as subjects only healthy young adults, since the Covid-19 mortality rate in this group is low. Just 7% of all Covid-19-related deaths in the U.S. have occurred among those aged 25 to 54 years, compared to 80% in those over age 65. Yet the example of fatal infections in health care workers in the prime of life makes clear that even healthy non-elderly adults may succumb to the novel coronavirus.

Human challenge studies are generally contemplated only when rescue with a lifesaving treatment or intervention is available should a vaccine candidate not protect a volunteer from the disease. But there is no cure or treatment against the SARS-CoV-2 virus that can be deployed with confidence, making viral challenge particularly risky and ethically questionable.

Most people, likely including most of the volunteers, tend to think of vaccines as fully effective: They either work or dont. This belief generally stems from the success of vaccines for childhood diseases like measles and mumps. But some vaccines, especially those for adults, are much less effective: There are seasons when the flu vaccine is only 70% to 80% effective, or sometimes even less. Imagine, for a moment, that a vaccine candidate undergoing testing turns out to generate immunity in 80% of those who receive it. Then 20% will become infected with Covid-19.

An equally disturbing scenario is what if one of the first volunteers dies, either due to the play of chance, a problem with the vaccine, or the individuals genetic makeup? This is unlikely to happen but it can, and did, in another setting with consequences that stretched far beyond the single tragic death.

In 1999, Jesse Gelsinger volunteered for one of the first gene therapy trials. The 18-year-old had a rare metabolic genetic disorder, but his condition was managed with medication; he was basically healthy. He volunteered for a safety trial of a virus-based gene-therapy and died as a result. Missteps in the trial, and the subsequent controversy surrounding his death, set the field of gene therapy back by at least two decades. That hiatus deprived a generation of patients with genetic disorders of treatments.

With vaccines already a target of widespread misinformation campaigns, the death of a single volunteer would likely cause even greater damage. From a public health perspective, it would be especially disastrous if it both slowed the race to develop a coronavirus vaccine and fueled the anti-vaccination movement.

There are other ethical considerations. An important principle in human challenge studies is that subjects must give their informed consent in order to take part. That means they should be provided with all the relevant information about the risk they are considering. But that is impossible for such a new disease.

Covid-19 was initially thought to be mainly a respiratory ailment. We now know that it can damage the kidneys, circulatory system, and the heart. It was initially believed that children could not be sickened by SARS-CoV-2, but it now appears that dozens have developed a severe inflammatory syndrome. And we know nothing about potential long-term complications of Covid-19 because the disease has only been in humans for months. Taken together, this means that no volunteer is able to give true informed consent.

Given these risks, there might still be some justification for a human challenge trial if we knew for certain it would accelerate the development of an effective vaccine. But safer trials can get us to a vaccine in the same amount of time without taking on additional risk for volunteers, especially now that some vaccine candidates already have entered Phase 2 clinical trials and several others are close behind.

In a conventional trial, subjects are injected with either the experimental vaccine or placebo. They are then monitored to see if those who got the vaccine are less likely to contract the disease while going about their daily lives. In a human challenge study, things can theoretically happen more quickly, since volunteers are deliberately infected after getting the trial vaccine or placebo.

But human challenge trials take time, too. For Covid-19, subjects would likely have to receive two doses of vaccine (spaced by weeks), wait for potential immunity to develop, then be infected with the live virus and observed for weeks to months. Since the challenge trial would need to start small and be expanded only with great caution because of the risks involved, it would take months to deliver sufficient data. Safety data, in particular, would be lacking, even though this is one of the biggest issues confronting a new vaccine, because the size of the trial would be too small to garner robust safety data and data about adverse effects of the vaccine would be confounded by the administration of the live virus.

There is no short cut for determining safety.

A large-scale, conventional study could likely be conducted just as quickly. In addition, monitoring and interim analyses of conventional trials raise the possibility of some kind of conditional or emergency use approval while the trials continue. If that happened, a vaccine might be available for certain high-risk or vulnerable groups in record time, namely 12 to 18 months from laboratory to clinic.

A final issue is that the results of the proposed human challenge studies come exclusively from the experience of younger adults, and cannot be extrapolated to the elderly, who tend to have weaker immune responses and the highest Covid-19 mortality rate. The volunteers might end up having risked their own health without truly helping those who are in greatest need of vaccine protection.

The world is overwhelmed by the pandemic. It is imperative to expedite development and approval pathways without forgoing safety and effectiveness. Ascertaining the risks intrinsic to the disease versus those of a new vaccine in specific populations health care workers, first responders, the elderly, those with comorbidities, and the like is essential. But acceleration should not mean forsaking ethical concerns, putting well-intentioned volunteers at needless risk, or setting back global vaccine efforts.

Michael Rosenblatt, M.D., is the chief medical officer of Flagship Pioneering, a venture firm that creates life sciences companies. He is the former chief medical officer of Merck and former dean of Tufts University School of Medicine. He serves as an adviser to Moderna, which is developing a Covid-19 vaccine; he is not a Moderna employee or shareholder. The opinions expressed are his own and do not necessarily reflect those of Flagship Pioneering or Moderna.

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Challenge trials aren't the answer to a speedy Covid-19 vaccine - STAT

Hitachi and ThinkCyte announce collaboration to develop an AI-driven cell analysis and sorting system – BioSpace

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TOKYO, July 1, 2020 /PRNewswire/ --Hitachi, Ltd.(TSE: 6501, "Hitachi") and ThinkCyte, Inc. ("ThinkCyte") today announced that they have entered into a collaboration focused on developing an artificial intelligence (AI)-driven cell analysis and sorting system. Hitachi provides a broad range of solutions such as automated cell culture technologies to pharmaceutical companies in the value chain*1 of the regenerative medicine and cell therapy industry. Through the addition of this cell analysis and sorting system to the value chain, Hitachi continues contributing to cost reductions in the manufacturing of regenerative medicine and cell therapy products.Further, Hitachi and ThinkCyte are promoting collaboration with pharmaceutical companies and research institutes working in the field of regenerative medicine and cell therapy to expedite the development of the system toward commercialization.

The practical applications of regenerative medicine and cell therapy using cells for treatment have been expanding rapidly with the first regulatory approval of CAR-T*2 therapy for leukemia in 2017 in the United States and 2019 in Japan. The global market for regenerative medicine and cell therapy is expected to grow from US$ 5.9 billion (JPY 630 billion) in 2020 to US$ 35.4 billion (JPY 3.8 trillion) in 2025*3. In order to scale up treatment using regenerative medicine and cell therapy products, it is critical to ensure consistent selection and stable supply of high quality cells in large quantities and at a low costs.

Hitachi has been providing large-scale automated induced pluripotent stem (iPS) cell culture equipment, cell processing facilities (CPFs), manufacturing execution systems(MES), and biosafety cabinets among other products to pharmaceutical companies and research institutes, and has developed a value chain to meet a variety of customer needs in the regenerative medicine and cell therapy industry. Hitachi has also been carrying out collaborative research projects with universities, research institutes, and other companies to develop core technologies for pharmaceutical manufacturing instruments and in vitro diagnostic medical devices, prototyping for mass production, and working on manufacturing cost reduction and the development of stable and reliable instruments.

ThinkCyte has been performing research and development focused on high-throughput single cell analysis and sorting technology to precisely analyze and isolate target cells. While such single cell analysis and sorting technologies are vital to life science and medical research, it has been thought impossible to achieve high-throughput cell sorting based on high-content image information of every single cell. ThinkCyte has developed the world's first Ghost Cytometrytechnology to achieve high-throughput and high-content single cell sorting*4and has been conducting collaborative research projects with multiple pharmaceutical companies and research institutes to utilize this technology in life science and medical fields.

Hitachi and ThinkCyte have initiated a joint development of the AI-driven cell analysis and sorting system based on their respective technologies, expertise, and know-how. By combining ThinkCyte's high-throughput and high-content label-free single cell sorting technology and Hitachi's know-how and capability to producing stably operative instruments on a large scale, the two companies will together develop a novel reliable system to enable high-speed label-free cell isolation with high accuracy, which has been difficult to achieve with the existing cell sorting techniques, and to realize stable, low-cost and large-scale production of cells for regenerative medicine and cell therapy.

Hitachi and ThinkCyte will further advance partnerships with pharmaceutical companies and research institutes that have been developing and manufacturing regenerative medicines and cell therapy products in Japan and other countries where demand is expected to be significant, such as North America, in order to make this technology a platform for the production of regenerative medicines and cell therapy products. At the same time, taking advantage of the high-speed digital processing technologies cultivated through the development of information and communication technology by the Hitachi group, Hitachi will integrate this safe and highly reliable instrument in its value chain for regenerative medicine and contribute to the growth of the regenerative medicine and cell therapy industry.

Note:

*1. Cell manufacturing processes, including cultivation, selection, modification, preservation, product quality control, etc.

*2. Chimeric Antigen Receptor T cells that have been genetically engineered to produce an artificial T-cell receptor for use in immunotherapy.

*3. Division of Regenerative Medicine, Japan Agency for Medical Research and Development, The final report for market research on regenerative medicine and gene therapy (2020).

*4. S, Ota et al., Ghost Cytometry, Science, 360, 1246-1251 (2018).

About the AI-driven cell analysis and cell sorting technologyThinkCyte has developed high-throughput image-based cell sorting technology based on the Ghost Cytometry technology by integrating the principles of advanced imaging technology, machine learning, and microfluidics. By applying structured illumination to cell imaging, structural information of a single cell can be converted to one-dimensional waveforms for high-throughput data analysis. Based on the judgment of a machine-learning (AI) model developed using the waveform data, target cells are isolated in a microfluidic device with high throughput and with minimal damage to the cells.

This data analysis approach eliminates time-consuming image reconstruction processes and allows high-throughput image-based single cell sorting, enabling the discrimination of cells that were previously considered difficult to distinguish by the human eye. Conventional cell sorting methods rely on the use of labels such as cell surface markers for cell sorting; in contrast, ThinkCyte's technology can sort cells without such labels by employing this unique approach. In addition to the field of regenerative medicine and cell therapy, this technology can also revolutionize drug discovery and in vitrodiagnostics fields.

About Hitachi, Ltd.Hitachi, Ltd. (TSE: 6501), headquartered in Tokyo, Japan, is focused on its Social Innovation Business that combines information technology (IT), operational technology (OT) and products. The company's consolidated revenues for fiscal year 2019 (ended March 31, 2020) totaled 8,767.2 billion yen ($80.4 billion), and it employed approximately 301,000 people worldwide. Hitachi drives digital innovation across five sectors - Mobility, Smart Life, Industry, Energy and IT - through Lumada, Hitachi's advanced digital solutions, services, and technologies for turning data into insights to drive digital innovation. Its purpose is to deliver solutions that increase social, environmental and economic value for its customers. For more information on Hitachi, please visit the company's website at https://www.hitachi.com.

About ThinkCyte, Inc.ThinkCyte, headquartered in Tokyo, Japan, is a biotechnology company, which developsinnovative life science research, diagnostics,and treatmentsusingintegrated multidisciplinary technologies, founded in 2016. The company focuses on the research and development of drug discovery, cell therapy, and diagnostic platforms using its proprietary image-based high-throughput cell sorting technology In June 2019, the company was selected for J-Startup by the Ministry of Economy, Trade and Industry of Japan. For more information on ThinkCyte, please visit the company's website at https://thinkcyte.com.

ContactsHitachi, Ltd.Analytical Systems Division, Healthcare Division, Smart Life Business Management Divisionhttps://www8.hitachi.co.jp/inquiry/healthcare/en/general/form.jsp

ThinkCyte, Inc.https://thinkcyte.com/contact

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Hitachi and ThinkCyte announce collaboration to develop an AI-driven cell analysis and sorting system - BioSpace

AI Applications for COVID-19 Research and Other News – Bio-IT World

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May 22, 2020 |A pair of studies demonstrate antibody responses to COVID-19 in primates. Researchers are applying artificial intelligence to lung images of COVID-19 patients. An accurate, easy-to-use, fully disposable, rapid and handheld test that consumers and healthcare providers in clinics can use to detect active SARS-CoV-2. We round up the weeks research and industry news for COVID-19.

Literature Updates

A pair of studies led by researchers at Beth Israel Deaconess Medical Center(BIDMC) were published in the journal Science. In the first study, the team demonstrated that six candidate DNA vaccines induced neutralizing antibody responsesand protected against SARS-CoV-2 in rhesus macaques. DOI: 10.1126/science.abc6284. In the second study, the team demonstrated that macaques that recovered from COVID-19 developed natural protective immunity against re-infection. Upon second exposure, the animals demonstrated near-complete protection against the virus. These data suggest natural protective immunity against COVID-19 in this model. DOI: 10.1126/science.abc4776.

Insilico Medicinehas co-authored a preprint paper with Nanome.aidescribing 10 potential small molecule inhibitors targeting the SARS-CoV-2 main protease that were generated by artificial intelligence (AI). The approach taken, called AI imagination, involves teaching a computer what the target protein looks like, letting it sniff out the binding pockets, and then imagine molecules with certain features having to do with the likelihood that a molecule will fit inside, and stay inside, a binding pocket. The AI-generated molecules are some of the first non-covalent drug candidates for COVID-19; non-covalent inhibitors are safer and more selective than covalent inhibitors. DOI: 10.13140/RG.2.2.13846.98881.

Researchers from the La Jolla Institute for Immunologyhave published the first cellular immunology data to help guide social distancing recommendations. Published in Cell, the study documents a robust antiviral immune response to SARS-CoV-2 in a group of 20 adults who had recovered from COVID-19. The findings show that the body's immune system is able to recognize SARS-CoV-2 in many ways, dispelling fears that the virus may elude ongoing efforts to create an effective vaccine. DOI: 10.1016/j.cell.2020.05.015.

Previous data from COVID-19 patients suggests that cigarette smokers are more likely to have health complications. One possible reason, researchers report in Developmental Cell, is that smoking increases the gene expression of ACE2the protein that binds SARS-CoV-2which may promote COVID-19 infection. The study suggests that prolonged smoking could cause an increase of the ACE2 protein in the lungs, possibly resulting in a higher rate of morbidity in patients. ACE2, or Angiotensin Converting Enzyme 2, is a regulatory protein that has been linked to vulnerability to the 2003 SARS (2003) virus. DOI: 10.1016/j.devcel.2020.05.

Researchers from the University of Trentohave published a novel fully-annotated dataset of lung ultrasonography (LUS) imagesfrom COVID-19 patients collected from several Italian hospitals, with labels indicating the degree of disease severity at a frame-level, video-level, and pixel-level (segmentation masks). Leveraging these data, they introduce a novel deep network, derived from Spatial Transformer Networks, which simultaneously predicts the disease severity score associated to an input frame and provides localization of pathological artefacts in a weakly-supervised way. They also benchmark state of the art deep models for estimating pixel-level segmentations of COVID-19 imaging biomarkers. Results were published in IEEE Transactions on Medical Imaging(Early Access). DOI: 10.1109/TMI.2020.2994459.

Leading immunologists in Japan reviewed two recent studies by Zhou et al. and Hoffmann et al. in order to understand their implications for finding effective therapeutic strategies for ARDSin COVID-19 patients. Based on their review, they are proposing a possible molecular mechanism that causes the massive release of proinflammatory cytokines, or a cytokine storm, that leads to acute respiratory distress syndrome (ARDS) in COVID-19 patients. Their suggestions are published in the journal Immunity. DOI: 10.1016/j.immuni.2020.04.003.

Mount Sinairesearchers are also applying artificial intelligence to lung images of COVID-19 patients. The Mount Sinai team has developed an algorithm that can rapidly detect COVID-19 based on how lung disease looks in computed tomography (CT scans) of the chest, in combination with patient information including symptoms, age, bloodwork, and possible contact with someone infected with the virus. This study, published in Nature Medicine, could help hospitals across the world quickly detect the virus, isolate patients, and prevent it from spreading during this pandemic. DOI: 10.1038/s41591-020-0931-3.

Patients infected with either severe acute respiratory syndrome coronavirus (SARS-CoV) or SARS-CoV-2 produce antibodies that bind to the other coronavirus, but the cross-reactive antibodies are not cross protective, at least in cell-culture experiments, researchers report in Cell Reports. Researchers analyzed blood samples collected from 15 SARS-CoV-2-infected patients in Hong Kong between 2 and 22 days after the onset of symptoms. Compared to blood samples from healthy controls, the five samples collected from patients 11 days after symptom onset or later had antibodies capable of binding to the RBD and other parts of the S protein on both SARS-CoV-2 and SARS-CoV. The researchers also analyzed blood samples collected from seven patients 3 to 6 months after infection with SARS-CoV. Compared to blood samples from healthy controls, those collected from patients had antibodies capable of binding to the RBD and other parts of the S protein on SARS-CoV-2. It remains unclear whether such antibodies offer cross protection in the human body or potentiate disease. DOI: 10.1016/j.celrep.2020.

An antibody called S309, first identified in a blood sample from a patient who recovered from Severe Acute Respiratory Syndrome in 2003, inhibits related coronaviruses, including SARS-CoV-2. The findings have been accepted for publication in Natureand the antibody is now on a fast-track development and testing path at Vir Biotechnology. It has not yet been shown to be protective in living systems. The S309 antibody is particularly potent at targeting and disabling the spike protein that promotes the coronavirus entry into cells. It was able to neutralize SARS CoV-2 by engaging with a section of the spike protein nearby the attachment site to the host cell. DOI: 10.1038/s41586-020-2349-y.

Industry Updates

Illuminaand the Illumina Corporate Foundation have committed more than $10M to COVID-19-related research and support. To support public health efforts associated with SARS-CoV-2 surveillance, sequencing and monitoring, Illumina is providing in kind donations valued at approximately $5M dollars for instruments and consumables. In addition, we dedicated more than $2M to COVID-19-related research efforts. To advance scientific research, Illumina, Inc. recently released the SARS-CoV-2 Data Toolkit, making it easier for researchers to detect and identify the viral sequence in their samples and contribute their findings to critical public databases. The toolkit is freely accessible on BaseSpace Sequence Hub until October 2020. Finally, the Illumina Foundation has awarded more than $3M in philanthropic donations, of which $1M has gone to the CDC Foundation COVID Emergency Response Fund, and $2M to local community-based initiatives in the areas where we operate. Press release.

Mammoth Biosciences and GSK Consumer Healthcareare collaborating to develop an accurate, easy-to-use, fully disposable, rapid and handheld testthat consumers and healthcare providers in clinics can use to detect active SARS-CoV-2. The collaboration will use Mammoth Biosciences CRISPR-based DETECTR platform that can identify and signal the presence of viral RNA strands obtained through a simple nasal swab. The test, which has the potential to deliver point-of-use results in less than 20 minutes, will be available first in the clinical setting and ultimately by consumers at home. Press release.

iSpecimenis partnering with myOnsite HealthCareto offer mobile phlebotomysupport that will bring convenient, at-home sample collection to patients and donors interested in advancing research who would otherwise have limited ability to participate. The mobile service extends iSpecimens ongoing mission to advance medical research by efficiently connecting researchers with patients, biospecimens, and the data they need to perform their important work. It also expands the companys recent initiatives to identify, collect, aggregate, manage, and ship specimens from COVID-19 patients. Press release.

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UBC scientist identifies a gene that controls thinness – UBC Faculty of Medicine – UBC Faculty of Medicine

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Why can some people eat as much as they want, and still stay thin?

In a study published today in the journal Cell, Life Sciences Institute Director Dr. Josef Penninger and a team of international colleagues report their discovery that a gene called ALK (Anaplastic Lymphoma Kinase) plays a role in resisting weight gain.

We all know these people, who can eat whatever they want, they dont exercise, but they just dont gain weight. They make up around one per cent of the population, says senior author Penninger, professor in the Faculty of Medicines department of medical genetics and a Canada 150 research chair.

Dr. Josef Penninger

We wanted to understand why, adds Penninger. Most researchers study obesity and the genetics of obesity. We just turned it around and studied thinness, thereby starting a new field of research.

Using biobank data from Estonia, Penningers team, including researchers from Switzerland, Austria, and Australia, compared the genetic makeup and clinical profiles of 47,102 healthy thin, and normal-weight individuals aged 20-44. Among the genetic variations the team discovered in the thin group was a mutation in the ALK gene.

ALKs role in human physiology has been largely unclear. The gene is known to mutate frequently in several types of cancer, and has been identified as a driver of tumour development.

Our work reveals that ALK acts in the brain, where it regulates metabolism by integrating and controlling energy expenditure, says Michael Orthofer, the studys lead author and a postdoctoral fellow at the Institute of Molecular Biology in Vienna.

When Penningers team deleted the ALK gene in flies and mice, both were resistant to diet-induced obesity. Despite consuming the same diet and having the same activity level, mice without ALK weighed less and had less body fat.

As ALK is highly expressed in the brain, its potential role in weight gain resistance make it an attractive mark for scientists developing therapeutics for obesity.

The team will next focus on understanding how neurons that express ALK regulate the brain at a molecular level, and determining how ALK balances metabolism to promote thinness. Validating the results in additional, more diverse human population studies will also be important.

Its possible that we could reduce ALK function to see if we did stay skinny, says Penninger. ALK inhibitors are used in cancer treatments already, so we know that ALK can be targeted therapeutically.

The study was supported by the Estonian Research Council, the European Union Horizon 2020 fund, and European Regional Development Fund, the von Zastrow Foundation, and the Canada 150 Research Chairs Program.

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Sarepta Therapeutics and Selecta Biosciences Enter into Research License and Option Agreement for Selecta’s ImmTOR Immune Tolerance Platform in…

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Application of ImmTOR plus Sareptas investigational gene therapies will be evaluated for Duchenne Muscular Dystrophy and Limb-Girdle Muscular Dystrophies

CAMBRIDGE, Mass. and WATERTOWN, Mass., June 18, 2020 (GLOBE NEWSWIRE) --Sarepta Therapeutics, Inc. (NASDAQ: SRPT), the leader in precision genetic medicine for rare diseases, and Selecta Biosciences, Inc. (NASDAQ: SELB) today announced that they have entered into a Research License and Option agreement granting Sarepta an option to license the rights to develop and commercialize Selectas immune tolerance platform, ImmTOR, for use in Duchenne muscular dystrophy (DMD) and certain limb-girdle muscular dystrophies (LGMDs). In advance of exercising its option, Sarepta will conduct research and evaluate the utility of ImmTOR to minimize or prevent the formation of neutralizing antibodies (NAb) to adeno-associated virus (AAV) in connection with the administration of Sareptas DMD and LGMD gene therapy candidates.

Sareptas late-stage gene therapy candidates are delivered using AAV in particular, AAVrh74. AAVrh74 was selected because of its safety profile, superior muscle tropism, empirical demonstration of high expression, and low screen-out rate for pre-existing antibodies. Currently, however, all systemic AAV-delivered constructs are one-time therapies that cannot be re-dosed due to the robust post-administration development of NAbs specific to the AAV vector. Selecta is a leader in immune tolerance and has generated strong preclinical evidence to support the potential for re-dosing patients receiving gene therapy.Selecta has reported that in preclinical studies, when used in combination with AAV gene therapy vectors,Selectas ImmTOR immune tolerance platform inhibits the development of NAbs to the vector, permitting re-dosing of the gene therapy. i

As we build our enduring gene therapy engine, we intend not only to rapidly advance treatments for rare, life-ending diseases, but at the same time, to advance the state of genetic medicine science by continually improving the utility of gene therapy. If successful, the ability to re-dose will be an enormous leap forward in the science of gene therapy and provide invaluable benefits to patients beyond those we anticipate with one-time dosing. We are encouraged by the data generated on the ImmTOR platform and excited to join with Selecta to explore the possibility of unlocking the opportunity to safely and effectively re-dose AAV-mediated gene therapies in patients with DMD and LGMDs, if needed, said Doug Ingram, President and Chief Executive Officer, Sarepta Therapeutics.

We are pleased to build on our already strong foundation of strategic partnerships and expand the clinical application of the ImmTOR platform into neuromuscular diseases. The ability to re-dose gene therapy addresses one of the major challenges of one-time therapies today, said Carsten Brunn Ph.D., President and Chief Executive Officer of Selecta Biosciences. We are excited to collaborate with a leader in genetic medicine like Sarepta, and are confident that their expertise in rare diseases combined with our immune tolerance platform has the potential to enhance the long-term therapeutic benefit to patients with these debilitating conditions.

DMD is a rare, degenerative neuromuscular disorder causing severe progressive muscle loss and premature death. LGMDs are a group of over 30 distinct diseases that cause weakness and wasting of the muscles around the hips and shoulders, eventually progressing to the arms and legs. LGMD can be caused by a single gene defect that affects specific proteins within the muscle cell, including those responsible for keeping the muscle membrane intact.

Under the terms of the research license and option agreement, Sarepta will make an initial payment to Selecta, and Selecta is eligible to receive certain pre-clinical milestone fees. If Sarepta exercises its options to enter any commercial license agreements, Selecta will be eligible for additional development, regulatory, and commercial milestone payments, as well as tiered royalties on net product sales. Additional financial details are not being disclosed.

About Selecta Biosciences, Inc.

Selecta Biosciences, Inc. is a clinical-stage biotechnology company focused on unlocking the full potential of biologic therapies based on its pioneering immune tolerance platform (ImmTOR). Selecta is committed to utilizing ImmTOR to potentially improve the efficacy of biologics, enable re-dosing of life-saving gene therapy, and create novel immunotherapies for autoimmune diseases. Selectas late-stage product candidate, SEL-212, is designed to be a monthly treatment for chronic refractory gout, a debilitating rare disease with a significant unmet medical need. SEL-212 consists of a combination of our ImmTOR platform co-administered with pegadricase, an enzyme designed to treat patients with symptomatic gout, refractory to standard uric acid lowering treatment. Selectas proprietary gene therapy product candidates are in development for certain rare inborn errors of metabolism and incorporate our ImmTOR platform with the goal of addressing barriers to repeat administration. In addition to our own pipeline of core discovery and clinical candidates, Selecta has established collaborative relationships with leading biopharmaceutical companies, including Asklepios BioPharmaceutical (AskBio) for gene therapy, and Swedish Orphan Biovitrum AB (Sobi) for SEL-212. Selecta is based in Watertown, Massachusetts. For more information, please visit http://www.selectabio.com.

Selecta Forward-Looking Statements:

SelectaBiosciences, Inc. (the company), including without limitation, the companys actions regarding the monitoring and assessment of COVID-19 on the companys operations, clinical trials and manufacturing, Sareptas plans to evaluate its gene therapies in combination with the companys ImmTOR technology, the possibility of Sarepta exercising an option to enter into a commercial license agreement, the unique proprietary technology platform of the company and the unique proprietary platform of its partners, the potential of ImmTOR to enable re-dosing of AAV gene therapy, the ability of the companys ImmTOR platform to unlock the full potential of biologic therapies, the potential treatment applications for product candidates utilizing the ImmTOR platform in areas such as enzyme therapy and gene therapy, the novelty of treatment paradigms that Sarepta is able to develop in combination with the companys ImmTOR technology, the potential of any therapies developed by Sarepta in combination with the companys ImmTOR technology to fulfill unmet medical needs, the companys plan to apply its ImmTOR technology platform to a range of biologics for rare and serious diseases, the ability of Sareptas existing therapies to target the heart and skeletal muscle, expected payments to be made to the company under the Research License and Option Agreement, the potential of the ImmTOR technology platform generally and the companys ability to grow its strategic partnerships, the sufficiency of the companys cash, cash equivalents and short-term investments, and other statements containing the words anticipate, believe, continue, could, estimate, expect, hypothesize, intend, may, plan, potential, predict, project, should, target, would, and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including, but not limited to, the following: the uncertainties inherent in the initiation, completion and cost of clinical trials including their uncertain outcomes, the effect of the COVID-19 outbreak on any of the companys planned or ongoing clinical trials, manufacturing activities, supply chain and operations, the availability and timing of data from ongoing and future clinical trials and the results of such trials, whether preliminary results from a particular clinical trial will be predictive of the final results of that trial or whether results of early clinical trials will be indicative of the results of later clinical trials, the unproven approach of the companys ImmTOR technology, Sareptas ability to research and develop therapeutic candidates using the companys ImmTOR technology, undesirable side effects of the companys product candidates, its reliance on third parties to manufacture its product candidates and to conduct its clinical trials as well as the impact of the COVID-19 outbreak on those third parties and their ability to continue their operations, the companys inability to maintain its existing or future collaborations, licenses or contractual relationships, its inability to protect its proprietary technology and intellectual property, managements ability to perform as expected, potential delays in regulatory approvals, Sareptas ability to make up-front and milestone payments, the companys business development strategy, the availability of funding sufficient for its foreseeable and unforeseeable operating expenses and capital expenditure requirements, the companys recurring losses from operations and negative cash flows from operations raise substantial doubt regarding its ability to continue as a going concern, substantial fluctuation in the price of its common stock including stock market fluctuations that occur as a result of the COVID-19 outbreak, and other important factors discussed in the Risk Factors section of the companys most recent Quarterly Report on Form 10-Q, and in other filings that the company makes with the Securities and Exchange Commission. In addition, any forward-looking statements included in this press release represent the companys views only as of the date of its publication and should not be relied upon as representing its views as of any subsequent date. The company specifically disclaims any intention to update any forward-looking statements included in this press release.

AboutSarepta Therapeutics

At Sarepta, we are leading a revolution in precision genetic medicine and every day is an opportunity to change the lives of people living with rare disease. The Company has built an impressive position in Duchenne muscular dystrophy (DMD) and in gene therapies for limb-girdle muscular dystrophies (LGMDs), mucopolysaccharidosis type IIIA, Charcot-Marie-Tooth (CMT), and other CNS-related disorders, with more than 40 programs in various stages of development. The Companys programs and research focus span several therapeutic modalities, including RNA, gene therapy and gene editing. For more information, please visitwww.sarepta.comor follow us onTwitter,LinkedIn,InstagramandFacebook.

Sarepta Forward-Looking Statement

This press release contains "forward-looking statements." Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as "believes," "anticipates," "plans," "expects," "will," "intends," "potential," "possible" and similar expressions are intended to identify forward-looking statements. These forward-looking statements include statements regarding the parties undertakings under the agreement and potential payments and fees; the potential benefits of Sareptas gene therapy product candidates; the potential of ImmTOR to enable re-dosing of AAV gene therapy; Sareptas intention to rapidly advance treatments for rare, life-ending diseases, and to advance the state of the genetic medicine science by continually improving the utility of gene therapy; the potential of re-dosing to provide invaluable benefits to patients beyond those Sarepta anticipates with one-time dosing;the possibility of unlocking the opportunity to safely and effectively re-dose AAV-mediated gene therapies in patients with DMD and LGMDs, if needed; and the potential of the collaboration between Sarepta and Selecta to enhance the long-term therapeutic benefit to patients with these debilitating conditions.

These forward-looking statements involve risks and uncertainties, many of which are beyond our control. Known risk factors include, among others: the expected benefits and opportunities related to the collaboration between Sarepta and Selecta may not be realized or may take longer to realize than expected due to challenges and uncertainties inherent in product research and development. In particular, the collaboration may not result in any viable treatments suitable for commercialization due to a variety of reasons, including any inability of the parties to perform their commitments and obligations under the agreement; success in preclinical trials does not ensure that later clinical trials will be successful; Sarepta may not be able to execute on its business plans and goals, including meeting its expected or planned regulatory milestones and timelines, clinical development plans, and bringing its product candidates to market, due to a variety of reasons, many of which may be outside of Sareptas control, including possible limitations of company financial and other resources, manufacturing limitations that may not be anticipated or resolved for in a timely manner, regulatory, court or agency decisions, such as decisions by the United States Patent and Trademark Office with respect to patents that cover Sareptas product candidates and the COVID-19 pandemic; and even if Sareptas programs result in new commercialized products, Sarepta may not achieve the expected revenues from the sale of such products; and those risks identified under the heading Risk Factors in Sareptas most recent Annual Report on Form 10-K for the year ended December 31, 2019, and most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) as well as other SEC filings made by Sarepta which you are encouraged to review.

Any of the foregoing risks could materially and adversely affect Sareptas business, results of operations and the trading price of Sareptas common stock. For a detailed description of risks and uncertainties Sarepta faces, you are encouraged to review the SEC filings made by Sarepta. We caution investors not to place considerable reliance on the forward-looking statements contained in this press release. Sarepta does not undertake any obligation to publicly update its forward-looking statements based on events or circumstances after the date hereof.

Selecta Contacts:For Media:Joshua R. MansbachSolebury Trout+1-646-378-2964jmansbach@soleburytrout.com

For Investors:Lee M. SternSolebury Trout+1-646-378-2922lstern@soleburytrout.com

Sarepta Contacts: Investors:Ian Estepan, 617-274-4052iestepan@sarepta.com

Media:Tracy Sorrentino, 617-301-8566tsorrentino@sarepta.com

_____________________________iNature Communications,October 2018.

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Sarepta Therapeutics and Selecta Biosciences Enter into Research License and Option Agreement for Selecta's ImmTOR Immune Tolerance Platform in...

Gene therapy: The ‘next generation’ of medicine – Irish Medical Times

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For people with rare diseases, a single gene therapy treatment could restore normal function and alleviate the burden of ongoing care, as Dr Ian Winburn tells Kennas Fitzsimons

Dr Ian Winburn

Gene therapy is the next generation of medicine that targets the underlying cause of genetic diseases. It has the potential to offer patients a really transformational clinical benefit and improve quality of life.

Thats according to Dr Ian Winburn, Global Medical Lead, Haemophilia, Endocrine and Inborn Errors of Metabolism (IEM), Rare Diseases, Pfizer Biopharmaceuticals Group. Dr Ian Winburn, Global Medical Lead, Haemophilia, Endocrine and IEM, Pfizer Biopharmaceuticals Group, pictured right during his presentation on gene therapy at BioPharma Ambition held in Dublin Castle on March 4. Pic: Conor McCabe Photography.

Formerly a clinician in the UK National Health Service (NHS), Dr Winburn trained in general surgery and completed a PhD on novel drug discovery in renal transplantation before moving into industry 10 years ago, where he worked in the area of inflammation and immunology before leading the European haemophilia team.

Dr Winburn is now working to develop innovative gene therapies with the potential to restore normal function to patients with rare diseases, possibly with just a single treatment, changing the way people manage their disease.

Gene therapy: What is it?Gene therapy uses genes as medicine. It works by introducing functioning copies of missing or defective genes into the body and can target the underlying cause of a disease at the cellular level.

There are various types of gene therapies, such as the gene editing technique, CRISPR (clustered regularly interspaced short palindromic repeats), as well as epigenetic approaches that look at ways in which genes may be turned on or turned off.

Pfizer Rare Disease is focusing on an in-vivo approach that utilises a recombinant adeno-associated virus (AAV) to deliver the gene therapy.

This approach works by targeting the missing or non-functional gene in an individuals DNA and adding a copy of it with a functioning gene that, in turn, produces a functioning protein.

The functioning gene serves as a blueprint for the tissue to create the missing or non-functioning protein that is causing a disease.

Dr Winburn said: Gene therapy is in the branch of genetic medicine, where you can think about approaches that look to add a gene to a host cell, and that gene goes on and codes for a protein. That protein its coding for can replace a missing protein. So, in the example of haemophilia, where theres a missing factor VIII or factor IX clotting factor, that protein that is either missing or is faulty could be essentially administered through a gene therapy. A gene is added to a host cell that codes for the factor VIII or factor IX and therefore replaces that protein.

The functioning gene is delivered directly to the targeted cells by means of a highly specialised viral vector. This vector, effectively, is the package that contains the gene. In simple terms, it can be likened to the cardboard boxes that online retailers use to ship products.

The manufactured vectors are protein shells modelled after viruses in which all infectious viral components have been removed, and a functioning gene is added. Different viral vectors are used to reach specific tissues in the body, such as the liver or muscle.

VectorVector is a great word because vector describes a direction, by definition, and the other way we can think about vector is a vector often carries something. There are a few approaches you can use to develop a vector. We have embraced an AAV vector that has the capacity to deliver the transgene, the gene that is going to be added to the host somatic cell. In the case of haemophilia, it is targeted at the liver, Dr Winburn says.

Rare diseases focusAbout 280 million people worldwide live with a genetic disease, and more than 80 per cent of rare diseases are genetic in origin, according to Pfizer. For people born with rare diseases, the burden of disease management can be huge. Treatment is often ongoing and may be lifelong. Gene therapy could enable patients to live without the need for ongoing treatment. This raises the prospect of relief not only from symptoms but also from the burden of disease management.

Dr Winburn elaborates on the reasons why gene therapy approaches are currently focused specifically on rare diseases that have single-gene alterations.

It tends to be rare genetic diseases that are monogenic in nature Some of the more common diseases are very much multifactorial in origin: there may be a genetic component but there are other aspects to their aetiology rather than these single, monogenic conditions that gene therapy really lends itself to.

The other aspect is that these are areas of huge unmet medical need. Often, there isnt a high standard of care with either medicines or clinical interventions that are ultimately influencing the progression and the symptoms of the disease, he says.

A lot of rare diseases often affect children by the very nature of their being of genetic origin. In some cases, children dont get the opportunity to grow up into adulthood because of these rare diseases. Having the opportunity to develop medicines where there is such a high level of unmet need and, ultimately, impact in a positive way the lives of families and their carers is a huge motivation.

Dr Winburn adds that rare diseases, collectively, are common. There are approximately 7,000 rare diseases, and the majority of these are of genetic origin. Gene therapy offers a groundbreaking technology to address these genetic diseases that have historically not had particularly strong standards of care or clinical treatment paradigms offered to them.

Gene therapy for haemophiliaPeople with the genetic disorder of haemophilia have insufficient levels of a clotting factor that helps to stop bleeding. Consequently, they bleed for longer than other people. The disease is typically treated through infusions of the missing clotting factor, with patients undergoing regular replacement therapy. Gene therapy could revolutionise this treatment model.

Its really important to put yourself in the position of a parent who has a young child who has haemophilia, Dr Winburn says.

Often, this disorder of coagulation that results in spontaneous bleeding due to the lack of functioning clotting factor first presents as early as the age of two, classically when children are becoming toddlers, when they start bumping into things and they develop bruising and the likes.

That alerts their parents attention to the possibility that there is something wrong with their clotting system and they [undergo] clinical tests and a diagnosis is made. Or, because its a genetic condition, it may run in families and parents are aware of the possibility of their newborn having haemophilia.

But if you are diagnosed, for example, at the age of two, it means that the mainstay of treatment is factor replacement. So, that commonly is an intravenous infusion possibly two to three times a week, possibly once a week, or once every other week, depending on whether its haemophilia A or B and what type of medicine is being prescribed. But its certainly frequent treatments. Again, if you put that back to a parent wholl be doing those infusions from the age of two or three that lifelong need and burden is huge.

While factor replacement enables children to live a full and active life to a degree, children with haemophilia may not necessarily get the opportunity to engage in all the activities children typically partake in as they are growing up, such as contact sports, Dr Winburn says.

There is this ongoing, lifelong burden of treatment. As those boys transition into adulthood, they often take responsibility for that and if they dont get their treatment then they will bleed spontaneously into their joints, they get problems with haemarthropathy, causing damage.

Ultimately, the incidence of joint damage and joint replacement surgeries is incredibly significant in the haemophilia population. And that is often despite optimal prophylaxis, where its being prescribed.

So, when you think about gene therapy, this is a single, one-off treatment with the potential to alleviate the need for regular infusion for a patient.

Not all patients will be eligible for a gene therapy or are being studied in gene therapy trials. This is not going to be something thats available for everybody. But for those that are eligible, and ultimately in disease where a gene therapy has been licensed by the regulator, this really does have the potential to massively impact their lives and give them a sense of normality that they havent necessarily had up until that point in time.

Future expectationsWhile gene therapy holds promise for many people with genetic diseases, it will not be an appropriate solution for every patient. The potential risks and benefits of gene therapy will be fully established through clinical trial programmes and with continued research and evaluation.

Patient safety and suitability are always primary considerations in the development of new treatments as they progress from preclinical and clinical testing through regulatory approval to potential commercial distribution. Dr Winburn stresses that, as regards the development of new gene therapies, patient safety is paramount.

Safety is always at the forefront of our thinking, it is the heart of our clinical trial programmes, it is the heart of all our regulatory work.

It is an ongoing process around evaluating safety, and particularly long-term safety, and there is a critical importance for all patients that ultimately receive a gene therapy to be followed up long-term within registries, within clinical databases, so that we can monitor and evaluate long-term safety. All our trials are designed so that safety outcomes are critically part of it and its something that we are ever watchful of.

For some patients, gene therapy is already a reality. There are currently a few rare diseases for which gene therapies are available as therapeutic options in Europe, and Dr Winburn anticipates that there may be up to 30 approved by 2023.

There is a rare congenital cause of blindness that currently has a gene therapy available and similarly a rare neurological condition that affects children also has a gene therapy available, thats spinal muscular atrophy (SMA). There is also a gene therapy for beta thalassaemia that has recently been approved and is available within Europe. In terms of haemophilia, the first gene therapy is currently under review in Europe.

It may be premature to imagine a scenario whereby gene therapy is used to treat chronic diseases more generally, but in terms of future applications for these emerging technologies it is a case of watch this space.

This is an area where we are definitely in breakthrough technology. At this moment in time, our focus has been on rare diseases. There is, of course, an interest in understanding what is possible with gene therapy in terms of where it could be utilised, Dr Winburn says.

I dont want to provide any false hopes, but I think aspirationally, there is a hope that this could certainly impact many patients and their families in a positive way.

In association with Pfizer Biopharmaceuticals Group.

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Gene therapy: The 'next generation' of medicine - Irish Medical Times

Novartis wins conditional EU approval for gene therapy Zolgensma – Reuters

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FILE PHOTO: The logo of Swiss drugmaker Novartis is pictured at the French company's headquarters in Rueil-Malmaison near Paris, France, April 22, 2020. REUTERS/Charles Platiau

ZURICH (Reuters) - Novartis won European approval for its gene therapy Zolgensma for the hereditary disease spinal muscular atrophy (SMA), the Swiss drugmaker said on Tuesday, adding it is in talks over price with countries in hopes of a quick launch.

The European Commission gave conditional approval to the therapy, whose U.S. price is $2.1 million, for patients with a clinical diagnosis of SMA Type 1, the most severe form of the disease, or SMA patients with up to three copies of a specific gene that helps doctors predict how severe the disease will be.

The EU approval covers babies and young children with SMA up to 21 kilograms. The medicine also has approval in Japan.

Novartis got Zolgensma with its $8.7 billion takeover of U.S.-based AveXis in 2018 and has forecast more than $1 billion in sales for the treatment, which in trials has been shown to significantly improve survival and motor function of babies with SMA, in particular those treated before symptoms develop.

Novartis said it is in talks with nations over what it calls its Day One access program, which the Basel-based drugmaker said is aimed at speeding up treatment by dealing with payment issues up front, even before national pricing and reimbursement agreements with individual countries are in place.

The Day One access program ensures the cost of patients treated before national pricing and reimbursement agreements are in place align with the value-based prices negotiated following clinical and economic assessments, Novartis said, adding the medicine will be immediately available in France.

Drug pricing in Europe varies from country to country, often relying on individual negotiations with regulators and pricing watchdogs that can slow down access, including in instances where officials conclude companies are seeking too much money for their medicines relative to the value they bring.

Reporting by John Miller; editing by Thomas Seythal and Brenna Hughes Neghaiwi

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Novartis wins conditional EU approval for gene therapy Zolgensma - Reuters

Are we wired for romance? – University of California

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If youve ever been a newlywed, you know the tingly euphoria of saying I do and starting a life with your spouse. This is romantic love, Western style. We often chalk it up to chemistry, an ill-defined connection of hearts and minds. Groundbreaking research at UC Santa Barbara finds we were closer than we knew.

For the first time, researchers have explored the neural and genetic connections to romantic love in newlyweds. By using functional magnetic resonance imaging (fMRI) and genetic analysis of 19 first-time newlyweds, Bianca Acevedo and her collaborators showed that romantic love maintenance is part of a broad mammalian strategy for reproduction and long-term attachment that is influenced by basic reward circuitry, complex cognitive processes and genetic factors.

In short, were hard-wired to sustain romantic love to maintain a successful marriage and the family unit, thanks to neurotransmitters like dopamine and a suite of genetic mutations.

This is the first study to examine the neural and genetic correlates of romantic love maintenance, said Acevedo, a research scientist at UC Santa Barbaras Department of Psychological & Brain Sciences and the lead author of After the Honeymoon: Neural and Genetic Correlates of Romantic Love in Newlywed Marriages in the journal Frontiers in Psychology.

The study showed that the maintenance of love is not only associated with activation of subcortical regions but also higher order centers of the brain, she said. Also, for the first time we provide evidence that the propensity to sustain romantic love may be affected by genetic variability. Specifically, the genes we examined are associated with pair-bonding behaviors including fidelity and sexual behaviors; and social behaviors such as trust, eye-gazing and attachment.

To test their hypothesis that romantic love is a developed form of the mammalian drive to find and keep mates, the researchers performed fMRI scans of the brains of the members of the study group 11 women and eight men. Participants were shown alternating images of their partners and a neutral acquaintance they knew well.

At the start of each session, the subjects were instructed to recall non-sexual events with the person whose face was displayed. While still in the scanner, participants rated their moods to verify that the evoked emotions corresponded to the target image.

The participants were tested around the time of marriage and a year later.

In addition, they provided saliva samples for testing of vasopressin, oxytocin and dopamine genes implicated in pair bonding in non-human mammals, such as voles.

Our findings showed robust evidence of the dopamine reward systems involvement in romantic love, Acevedo said. This system is interesting because it is implicated in motivation, energy, working for rewards, and is associated with corresponding emotions such as excitement, euphoria and energy, as well as frustration if the drive is thwarted.

Acevedos current research builds on her work on empathy and altruism and its correlates in the brain.

Empathy has its roots in social bonding, she explained. In our previous work we showed that although humans express sentiments such as empathy and altruism towards strangers and non-close others, brain responses to partners are stronger. Thus, there is specificity. Romantic love is somewhat different in that it may or may not include empathy or altruism, but in healthy partnerships it does.

For some romantics, it might seem a tad clinical to chalk up our feelings of love and commitment to biochemistry. Acevedo, however, said gene mutations and brain activity are only components of romance and belonging.

Humans are creative and clever, she said. Romantic love inspires people to know how to put a smile on their partners face. By making our partners happy we not only keep our relationships stable, but we also derive joy from such events.

In the brain, Acevedo continued, this is shown as increased reward activation when people are shown images of a partner smiling and they are told that something wonderful has happened to the partner. People know this intuitively. They know that romance goes a long way in finding and keeping a preferred mate. Thats why there is multibillion-dollar industry built on it from dating sites, to lingerie to Hallmark cards, chocolate and diamond rings.

And besides, our chemical impulses dont buy flowers or cook dinner.

Love is basic but complex, Acevedo said. We are wired to love, but it takes work to find and keep love alive."

Nancy L. Collins, a professor in UC Santa Barbaras Psychological and Brain Sciences, was a co-author of After the Honeymoon. She is also director of the UC Santa Barbara Close Relationship Lab. Other authors are Michael J. Poulin of the University of Buffalo and Lucy L. Brown of the Albert Einstein College of Medicine in New York.

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Are we wired for romance? - University of California

Vertex Receives European CHMP Positive Opinion for KALYDECO (ivacaftor) for Children and Adolescents With Cystic Fibrosis Between the Ages 6 Months…

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LONDON--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that the European Medicines Agencys (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for the label extension of KALYDECO (ivacaftor), to include the treatment of children and adolescents with cystic fibrosis (CF), ages 6 months and older weighing at least 5 kg who have the R117H mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

Todays announcement is important for young people with CF, as early intervention and treatment of this devastating and progressive disease is key to keeping patients healthier longer, said Carmen Bozic, M.D., Executive Vice President and Chief Medical Officer at Vertex. This milestone also brings us one step closer to achieving our ultimate goal of bringing medicines forward to all people with CF.

The European Commission will now review the CHMPs positive opinion, and should they issue a favorable adoption, KALYDECO (ivacaftor) will be the first and only approved medicine in Europe to treat the underlying cause of CF in patients ages 6 months and older with the R117H mutation. In countries where long-term reimbursement agreements have been secured, KALYDECO (ivacaftor), if approved, would be available to eligible patients shortly after Marketing Authorization. In Germany, the medicine would be available at Marketing Authorization. In all other countries, we will work closely with relevant authorities in Europe to secure access for eligible patients quickly.

In Europe, KALYDECO (ivacaftor) is already approved for the treatment of people with CF ages 18 and older with the R117H mutation, and children ages 6 months and older weighing at least 5 kg who have one of the following mutations in the CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N or S549R.

About Cystic Fibrosis

Cystic Fibrosis (CF) is a rare, life-shortening genetic disease affecting approximately 75,000 people worldwide. CF is a progressive, multi-system disease that affects the lungs, liver, GI tract, sinuses, sweat glands, pancreas and reproductive tract. CF is caused by a defective and/or missing CFTR protein resulting from certain mutations in the CFTR gene. Children must inherit two defective CFTR genes one from each parent to have CF. While there are many different types of CFTR mutations that can cause the disease, the vast majority of all people with CF have at least one F508del mutation. These mutations, which can be determined by a genetic test, or genotyping test, lead to CF by creating non-working and/or too few CFTR proteins at the cell surface. The defective function and/or absence of CFTR protein results in poor flow of salt and water into and out of the cells in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus that can cause chronic lung infections and progressive lung damage in many patients that eventually leads to death. The median age of death is in the early 30s.

About KALYDECO (ivacaftor)

Ivacaftor is the first medicine to treat the underlying cause of CF in people with specific mutations in the CFTR gene. Known as a CFTR potentiator, ivacaftor is an oral medicine designed to keep CFTR proteins at the cell surface open longer to improve the transport of salt and water across the cell membrane, which helps hydrate and clear mucus from the airways.

About Vertex

Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has multiple approved medicines that treat the underlying cause of cystic fibrosis (CF) a rare, life-threatening genetic disease and has several ongoing clinical and research programs in CF. Beyond CF, Vertex has a robust pipeline of investigational small molecule medicines in other serious diseases where it has deep insight into causal human biology, including pain, alpha-1 antitrypsin deficiency and APOL1-mediated kidney diseases. In addition, Vertex has a rapidly expanding pipeline of genetic and cell therapies for diseases such as sickle cell disease, beta thalassemia, Duchenne muscular dystrophy and type 1 diabetes mellitus.

Founded in 1989 in Cambridge, Mass., Vertex's global headquarters is now located in Boston's Innovation District and its international headquarters is in London, UK. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia and Latin America. Vertex is consistently recognized as one of the industry's top places to work, including 10 consecutive years on Science magazine's Top Employers list and top five on the 2019 Best Employers for Diversity list by Forbes.

Special Note Regarding Forward-looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, Dr. Bozics statements in the second paragraph of this press release, and statements regarding our expectations for the approval and availability of KALYDECO in Europe, and our plans for securing access to KALYDECO for eligible patients in Europe. While Vertex believes the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company's beliefs only as of the date of this press release and there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that data from the company's development programs may not support registration or further development of its compounds due to safety, efficacy or other reasons, risks related to obtaining and commercializing KALYDECO in Europe, and other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through the company's website at http://www.vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

(VRTX-GEN)

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Vertex Receives European CHMP Positive Opinion for KALYDECO (ivacaftor) for Children and Adolescents With Cystic Fibrosis Between the Ages 6 Months...

Sarepta Therapeutics to Announce First Quarter 2020 Financial Results and Recent Corporate Developments on May 6, 2020 – GlobeNewswire

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CAMBRIDGE, Mass., April 29, 2020 (GLOBE NEWSWIRE) -- Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, will report first quarter 2020 financial results after the Nasdaq Global Market closes on Wednesday, May 6, 2020. Subsequently, at 4:30 p.m. E.T., the Company will host a conference call to discuss its first quarter 2020 financial results and to provide a corporate update.

The conference call may be accessed by dialing (844) 534-7313 for domestic callers and (574) 990-1451 for international callers. The passcode for the call is 2553748. Please specify to the operator that you would like to join the "Sarepta First Quarter 2020 Earnings Call." The conference call will be webcast live under the investor relations section of Sarepta's website at http://www.sarepta.com and will be archived there following the call for 90 days. Please connect to Sarepta's website several minutes prior to the start of the broadcast to ensure adequate time for any software download that may be necessary.

AboutSarepta TherapeuticsAt Sarepta, we are leading a revolution in precision genetic medicine and every day is an opportunity to change the lives of people living with rare disease. The Company has built an impressive position in Duchenne muscular dystrophy (DMD) and in gene therapies for limb-girdle muscular dystrophies (LGMDs), mucopolysaccharidosis type IIIA, Charcot-Marie-Tooth (CMT), and other CNS-related disorders, with more than 40 programs in various stages of development. The Companys programs and research focus span several therapeutic modalities, including RNA, gene therapy and gene editing. For more information, please visitwww.sarepta.com or follow us on Twitter, LinkedIn, Instagram and Facebook.

Internet Posting of Information

We routinely post information that may be important to investors in the 'For Investors' section of our website atwww.sarepta.com. We encourage investors and potential investors to consult our website regularly for important information about us.

Source: Sarepta Therapeutics, Inc.

Sarepta Therapeutics, Inc.

Investors:Ian Estepan, 617-274-4052iestepan@sarepta.com

Media:Tracy Sorrentino, 617-301-8566tsorrentino@sarepta.com

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Sarepta Therapeutics to Announce First Quarter 2020 Financial Results and Recent Corporate Developments on May 6, 2020 - GlobeNewswire

One-of-a-Kind Coronavirus Was Artificially Produced? – The Liberty Web English

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Interview

We asked a U.S. expert, specialized in poison and biochemistry, about the origin and motive behind the coronavirus. His books include Overall View of Chemical and Biological Weapons published in 2001.

Colorado State UniversityProfessor Emeritus

Dr. Anthony Tu

Born in Taipei in 1930. After graduating from National Taiwan University under Japanese rule, Tu studied biochemistry at the University of Notre Dame, Stanford University and Yale University.

I believe theres a high possibility that the Wuhan virus was created artificially. I rule out the theory that the coronavirus was originated naturally because a bat-borne virus doesnt transfer naturally to other people.

Shi Zhenglis research team at the Wuhan Institute of Virology of the Chinese Academy of Sciences in Wuhan has been researching the transmission of bat-borne SARS viruses across species. In November 2015, five years before the coronavirus pandemic, she published in Nature Medicine (*1) about her successful experiment of manipulating the SARS virus to have harmful effects on mice respirators.

Although the Wuhan virus is based on the bat-borne SARS virus, the genetic sequence is slightly different than that of SARS. Research done by Professor Pradhan of India have found that the HIV and the Wuhan virus have similar protuberances. The coronavirus has been developed to infect people easier by artificially inserting four HIV-derived gene sequences into the genetic sequence of the SARS virus.

In terms of their research motive, it certainly could be for vaccine development. However, it is unnatural to develop a vaccine for a virus that is not widespread. Another speculation in the U.S. is the biological weapons theory. Although there remains uncertainty since Chinas hasnt confessed, we can naturally assume from research articles that the Wuhan virus was developed as a biological weapon and the artificially-developed coronavirus was accidentally leaked from their research facility.

Dr. Shis paper also suggested an application on primates. At the time, this led to heated debates in Europe and the U.S. French researchers warned that if the virus escapes, nobody could predict the trajectory. (*2) The coronavirus spread all over the world just as they warned. It can also converge and become an epidemic again.

I have suggested from early on that it is best to send out hospital ships and quarantine people there. Once the hospital is infected, the infection will spread widely. There are 35 ships in the U.S., and each ship can hold 1,000 patients. Japan is demanded to take such measures.

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One-of-a-Kind Coronavirus Was Artificially Produced? - The Liberty Web English

Headaches After Exercise? Its Linked to Your Intensity, New Research Suggests – runnersworld.com

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If youre prone to migraines, you may have heard that exercise can decrease their frequency and improve their symptoms, based on previous research about how activity can reduce migraine triggers. But a recent study in Clinical Chemistry and Laboratory Medicine adds an important caveat to that advice: Watch your intensity.

Researchers looked at 48 male amateur runners, who ran a half-marathon distance at 75 to 85 percent of maximal oxygen uptakea measure of their running intensity.

Before and after running, participants had blood drawn to determine their levels of calcitonin gene-related peptide (CGRP), a compound in your body responsible for triggering physical reactions like vasodilationdilation of your blood vessels, which increases blood pressureand inflammation in your nervous system. CGRP levels is often associated with headache pain, especially migraines.

The concentration of the compound was significantly increased in the entire group, and those who were prone to headaches reported suffering from one after the run. That led researchers to conclude that medium-distance endurance exercise is a booster for CGRP, and that high-intensity exercise can heighten that reaction even morepotentially triggering both migraines and headaches brought on by exertion.

Does that mean if youre a headache sufferer, you need to find a different activity? Thankfully, no. But you may need to dial back the intensity in your running, study author Fabian Sanchis-Gomar, M.D., Ph.D., of the Division of Cardiovascular Medicine at Stanford University Medical Center told Runners World. Low-to-moderate exercise doesnt seem to be as much of a trigger, he said.

[Run faster, stronger, and longer with this 360-degree training program.]

If thats not an option, he suggested talking with a doctor about migraine preventive therapy, since that often involves medication that blocks the CGRP receptor specifically. Although this study didnt cover whether runners on that medication would still get migraines, Sanchis-Gomar suggested that its likely they wouldnt, because even though the CGRP would surge, the receptors would block it enough to reduce the risk of headache pain.

For those who arent prone to migraines, though, keep on trucking: CGRP increases are actually a good thing for you.

High-intensity exercise represents an insult [interruption of blood flow] for the cardiovascular system: increasing blood pressure, said Sanchis-Gomar. CGRP counteracts this and has a protective effect for cardiovascular function.

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Headaches After Exercise? Its Linked to Your Intensity, New Research Suggests - runnersworld.com

UW researchers collaborate with New York doctors for improved COVID-19 treatments – The Badger Herald

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The Albany Medical Center in New York and University of Wisconsin researchers are collaborating to find a way to better allocate medical resources to COVID-19 patients using mass spectrometry techniques.

According to a UW press release, Dr. Ariel Jaitovich, a pulmonary and critical care physician at the Albany Medical Center, reached out to UW researchers for improving treatment and care for COVID-19 patients.

Its a new disease. Two months ago, we knew nothing about it, Dr. Jaitovich said in the release. What we are trying to do now is do systematic work to better understand what this disease is about.

UW researchers create survey to understand community beliefs, behaviors amid COVID-19 pandemicWith the help of the League of Wisconsin Municipalities, University of Wisconsin released a research survey tracking peoples current behaviors Read

The team is comprised of the Albany Medical Center in New York, Morgridge Institute for Research and the Department of Biomolecular Chemistry at the UW School of Medicine and Public Health, according to the release.

SMPH professor Josh Coon, who specializes in mass spectrometry research, is working together with the research group to contrast samples from COVID-19 patients with control samples of those who have tested negative for the virus. The team will analyze about 150 samples from the Albany Medical Center to understand the molecular profile of COVID-19, according to the press release.

UW professionals discussed transmission of, responses to COVID-19 through online panelAs part of the Crossroads of Ideas lecture series, UW professionals discussed transmission of and responses to COVID-19 on Tuesday, Read

This is extremely important for many reasons, because you can, for example, intervene early with people who are more likely to do worse over time based on these early identified markers, Coon said inthe release. You can better allocate resources in a moment in which there is a shortage of resources to deal with this pandemic.

Coon said mass spectrometry can provide molecular signals that can then help in distinguishing between mild and severe cases. Coon also said some possible indicators of the severity of the disease could be blood clotting factors in lung vessels and cytokine storms that trigger the immune systems inflammatory response to skyrocket and result in acute respiratory distress syndrome, according to the release.

UW research team analyzes travel, social media data to monitor COVID-19 spreadA multidisciplinary research team, headed by University of Wisconsin professor Song Gao, started analyzing travel and social media data to Read

The Coon Laboratory is investigating the molecular signals of the disease and Jaitovichs team in New York is examining the potential genetic influences on COVID-19 through RNA sequencing by collaborating with Associate Director of Bioinformatics Ron Stewart and computational biologist Scott Swanson at the Morgridge Institute for Research.

We should be able to get an idea about what genes or gene sets are involved in things like inflammation, and how that might differ between COVID-19 and other ARDS cases, Stewart said in the release.

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UW researchers collaborate with New York doctors for improved COVID-19 treatments - The Badger Herald

Innovation Wrap: Microscopic Robots, Asteroid Mining, A Flurry Of IPOs – ShareCafe

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Heres your wrap of the latest technology, innovation, and finance news.

Robotics

UPenn researchers are building an army of microscopic robots. One day they could help us explore the world, or the human body, at a microscopic scale.

Through a process similar to that used in creating circuit boards, Miskin and his team were able to mass-produce more than a million of the microrobots, each of which is smaller than a tenth of a millimetre and is only visible under a microscope.

Spot has found a new job. Ford Motor Company is using two of the dog-like robots to map out their 200,000 square-metre Van Dyke Transmission Plant in Detroit. The data will be used to create a digital twin of the facility that will help Ford engineers better plan out process improvements, at a lower cost than traditional methods.

Over the years, factory plans get out of date as things are moved around and new equipment is brought in. Surveying the transmission plant by hand would take weeks and cost some $300,000. Ford reckons that Fluffy and Spot, which can both climb stairs and crawl into hard-to-reach areas, will cut the time required by half and complete the job for a fraction of the cost.

Biology

Harvard University researchers are helping mice keep weight off by using gene-editing to turn some of their regular white fat cells into energy-burning brown fat cells (see their paper).

In the future, this technique could potentially be used to treat people affected by obesity and metabolic disorders, says Tseng. It could be possible to remove a small amount of a persons white fat, engineer it into brown-like fat and re-implant it, she says.

Synthego, an AI-driven gene-editing startup founded by former SpaceX engineers, has raised $100 million.

Synthegos tools all of which are cloud-hosted cover over 120,000 genomes and 9,000 species. They provide guides to knock out genes with ostensibly minimal collateral effects. Underlying machine learning models predict overall editing efficiencies and even the set of mutations created for any given edit. Guide RNAs and cell engineering services for mammalian cell lines, primary cells, and more aid with editing experiments, along with guides that can be modified to resist degradation and prevent damaging immune responses.

Health

Stanford University researchers have found a way to wake dormant stem cells and grow new cartilage in the joints of arthritic mice (see their paper).

Primitive cells that can be transformed into new cartilage lie dormant at the ends of bones, the researchers reported in Nature Medicine. The cells just have to be awakened and stimulated to grow.

There is no cure for herpes, but were one step closer after researchers used gene therapy to significantly decrease latent infections in mice (see their paper).

This is the first time that anybody has been able to go in and actually eliminate most of herpes in a body, said Jerome, who is also spearheading research at Fred Hutch and the University of Washington on COVID-19. It is a completely different approach to herpes therapy than anybodys ever had before.

Gaming

CD Projekt announced a new mobile augmented reality game, The Witcher: Monster Slayer which is reminiscent of Pokmon Go. CD Projekts stock rose 7% on the day.

Are you familiar with Roblox? The Economist highlighted the game as one of the biggest entertainment success stories of the pandemic with more than 164 million active users and 2m+ creators.

Roblox is not itself a video game, but rather a game-creation platform. Users can design and build their own games and worlds using icons and pre-fabricated Lego-like blocks, rather than code, and then easily share them with friends.

Felipe Pepe concluded that Roblox is a MUD for the TikTok generation in a fascinating history of MUDs, virtual worlds, and MMORPGs. I spent a good deal of time playing MUDs growing up (and first learnt to program in one), so theyll always have a special place in my heart.

Renewables

The UK government has reduced its estimate of 2025 wind and solar costs by 30-50%.

The reasons for the renewable cost reductions are well documented. They include technological learning in the industry with larger, more efficient manufacturing plants for solar and larger turbines for wind but also operational experience, longer project lifetimes and cheaper finance.

French renewables developer Neoen is planning a $3 billion wind, solar, and storage project in South Australia.

The plan proposes a total of 1,200MW of wind energy, 600MW of solar PV, and 900MW/1800MWh of battery storage, an extremely large battery as Neoen describes it that will dwarf the 150MW/194MWh Tesla battery known officially as the Hornsdale Power Reserve.

Finance

Even great scientists like Sir Isaac Newton can get caught up in bubbles.

Newton had a simple explanation for his lapse. At the crucial moment, hed lost his mind. Or rather, others around him had lost theirs. I can calculate the motions of the heavenly bodies, his niece recalled him saying, but not the madness of the people.

It must be IPO season! Several companies filed for IPO (or a direct listing) fintech giant Ant Group, game engine developer Unity Software (S-1), data warehouse company Snowflake (S-1), data analytics company Palantir Technologies (S-1), work management tool Asana (S-1), business intelligence software company Sumo Logic (S-1), and developer tool company JFrog (S-1).

Other Snippets

DARPAs AlphaDogfight trials concluded with an AI pilot winning a flawless victory against a highly-trained US Air Force F-16 pilot.

Stratechery wrote a good summary of why Australias News Media Bargaining Code makes no sense.

Google released the alpha version of Jetpack Compose, which promises to let Android developers write apps with dramatically less code.

K-pop continues to break YouTube viewing records with BTSs new music video for Dynamite racking up 98 million views within 24 hours. This surpassed previous record Blackpink which saw 86 million views within 24 hours for How You Like That back in June.

Kurzgesagt explained the basics of asteroid mining.^

^ Well, kind of As Troy McCann, founder of space startup accelerator Moonshot, correctly points out, asteroid mining will focus on the use of the materials in space, not on earth, given materials in space are always more valuable than those on earth as they embed the cost to get the material there. As such, this video doesnt really represent early asteroid mining efforts which are more likely to focus on water in space rather than delivering material to earth.

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Innovation Wrap: Microscopic Robots, Asteroid Mining, A Flurry Of IPOs - ShareCafe

Study reveals genetic mutations may be linked to infertility, early menopause – Devdiscourse

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A new study identifies a specific gene's previously unknown role in fertility. Analysing genetic data in people, the researchers found an association between mutations in this gene and early menopause. The study appears in the journal of Science Advances.

The human gene -- called nuclear envelope membrane protein 1 (NEMP1) -- is not widely studied. In animals, mutations in the equivalent gene had been linked to impaired eye development in frogs. When the gene is missing in fruit flies, roundworms, zebrafish and mice, the animals are infertile or lose their fertility unusually early but appear otherwise healthy. The researchers who made the new discovery were not trying to study fertility at all. Rather, they were using genetic techniques to find genes involved with eye development in the early embryos of fruit flies.

"We blocked some gene expression in fruit flies but found that their eyes were fine," said senior author Helen McNeill, PhD, the Larry J. Shapiro and Carol-Ann Uetake-Shapiro Professor and a BJC Investigator at the School of Medicine. "So, we started trying to figure out what other problems these animals might have. They appeared healthy, but to our surprise, it turned out they were completely sterile. We found they had substantially defective reproductive organs." Though it varied a bit by species, males and females both had fertility problems when missing this gene. And in females, the researchers found that the envelope that contains the egg's nucleus -- the vital compartment that holds half of an organism's chromosomes -- looked like a floppy balloon.

"This gene is expressed throughout the body, but we didn't see this floppy balloon structure in the nuclei of any other cells," said McNeill, also a professor of developmental biology. "That was a hint we'd stumbled across a gene that has a specific role in fertility. We saw the impact first in flies, but we knew the proteins are shared across species. With a group of wonderful collaborators, we also knocked this gene out in worms, zebrafish and mice. It's so exciting to see that this protein that is present in many cells throughout the body has such a specific role in fertility. It's not a huge leap to suspect it has a role in people as well." To study this floppy balloon-like nuclear envelope, the researchers used a technique called atomic force microscopy to poke a needle into the cells, first penetrating the outer membrane and then the nucleus's membrane. The amount of force required to penetrate the membranes gives scientists a measure of their stiffness. While the outer membrane was of normal stiffness, the nucleus's membrane was much softer.

"It's interesting to ask whether stiffness of the nuclear envelope of the egg is also important for fertility in people," McNeill said. "We know there are variants in this gene associated with early menopause. And when we studied this defect in mice, we see that their ovaries have lost the pool of egg cells that they're born with, which determines fertility over the lifespan. So, this finding provides a potential explanation for why women with mutations in this gene might have early menopause. When you lose your stock of eggs, you go into menopause." McNeill and her colleagues suspect that the nuclear envelope has to find a balance between being pliant enough to allow the chromosomes to align as they should for reproductive purposes but stiff enough to protect them from the ovary's stressful environment. With age, ovaries develop strands of collagen with the potential to create mechanical stress not present in embryonic ovaries.

"If you have a softer nucleus, maybe it can't handle that environment," McNeill said. "This could be the cue that triggers the death of eggs. We don't know yet, but we're planning studies to address this question." Over the course of these studies, McNeill said they found only one other problem with the mice missing this specific gene: They were anaemic, meaning they lacked red blood cells.

"Normal adult red blood cells lack a nucleus," McNeill said. "There's a stage when the nuclear envelope has to condense and get expelled from the young red blood cell as it develops in the bone marrow. The red blood cells in these mice aren't doing this properly and die at this stage. With a floppy nuclear envelope, we think young red blood cells are not surviving in another mechanically stressful situation." The researchers would like to investigate whether women with fertility problems have mutations in NEMP1. To help establish whether such a link is causal, they have developed human embryonic stem cells that, using CRISPR gene-editing technology, were given specific mutations in NEMP1 listed in genetic databases as associated with infertility.

"We can direct these stem cells to become eggs and see what effect these mutations have on the nuclear envelope," McNeill said. "It's possible there are perfectly healthy women walking around who lack the NEMP protein. If this proves to cause infertility, at the very least this knowledge could offer an explanation. If it turns out that women who lack NEMP are infertile, more research must be done before we could start asking if there are ways to fix these mutations -- restore NEMP, for example, or find some other way to support nuclear envelope stiffness." (ANI)

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Our genes know kindness is the best medicine – Brainerd Dispatch

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Editor's note: Life can be stressful, and many of us have a hard time administering self-care. The current world situation ripe with conflicts, shortages and a pandemic makes things even harder. Dr. Amit Sood, formerly of Mayo Clinic and now head of the Global Center for Resiliency and Wellbeing, is the author of books including "The Mayo Clinic Handbook for Happiness" and "SMART with Dr. Sood, and creator of the mobile app Zizo: Your Resilience Pal. Now, he is writing a weekly column answering readers' questions on these topics. See the tagline to learn how to send him your questions, and he will answer in future columns.

Dear friend,

Of the hundreds of ice-creams I have eaten so far, the only one I remember is the ice-cream I never ate.

That was in 1993. My wife Richa and I were sitting outside a shop in the sweltering New Delhi. We had just bought an ice cream to cool down. From the corner of my eye, I saw a little boy who could use a few calories. I walked up to him and offered my cone that he gladly took. I have savored the gleam I saw in his eyes at least a dozen times since then.

In a very interesting study, researchers looked at the genetic fingerprint of the two types of happiness hedonistic (self-centric) and eudaimonic (other-centric). People who were hedonistically happy had a higher inflammatory and lower anti-viral gene expression. It was just the opposite for the eudaimonic ones. With many illnesses caused by inflammation, you can see why this is so important for our health.

My take on this research is that our genes and the immune system know what is right for us and society. In the current times when a healthy immune system is extremely important for us, promoting kindness is imperative.

Kindness, research shows, pays three times over. Your kind words and actions enhance your health and wellbeing, help others, and the memory of kind actions by itself enhances your wellbeing. A very simple way to enhance your self-worth and happiness today is to count your previous kind actions.

I suggest take out a pen and paper and write the three most selfless things you have done in your life. If you feel up to it, share your experience with someone. Just counting previous acts of kindness can enhance your self-worth and bring happiness to others (you guessed it right witnessing or hearing about others kind actions also increases happiness).

In kindness,

Amit

Dr. Amit Sood answers your questions about stress, resilience, happiness, relationships, and related topics in his column. Email dearfriend@postbulletin.com.

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Case Western Reserve University-led team develops new approach to treat certain neurological diseases – Mirage News

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A team led by Case Western Reserve University medical researchers has developed a potential treatment method for Pelizaeus-Merzbacher disease (PMD), a fatal neurological disorder that produces severe movement, motor and cognitive dysfunction in children. It results from genetic mutations that prevent the body from properly making myelin, the protective insulation around nerve cells.

Paul Tesar, professor of genetics and genome sciences, School of Medicine

Using mouse models, the researchers identified and validated a new treatment target-a toxic protein resulting from the genetic mutation. Next, they successfully used a family of drugs known as ASOs (antisense oligonucleotides) to target the ribonucleic acid (RNA) strands that created the abnormal protein to stop its production. This treatment reduced PMDs hallmark symptoms and extended lifespan, establishing the clinical potential of this approach.

By demonstrating effective delivery of the ASOs to myelin-producing cells in the nervous system, researchers raised the prospect for using this method to treat other myelin disorders that result from dysfunction within these cells, including multiple sclerosis (MS).

Their research was published online July 1 in the journal Nature.

The pre-clinical results were profound. PMD mouse models that typically die within a few weeks of birth were able to live a full lifespan after treatment, said Paul Tesar, principal investigator on the research, a professor in the Department of Genetics and Genome Sciences at the School of Medicine and the Dr. Donald and Ruth Weber Goodman Professor of Innovative Therapeutics. Our results open the door for the development of the first treatment for PMD as well as a new therapeutic approach for other myelin disorders.

Study co-authors include an interdisciplinary team of researchers from the medical school, Ionis Pharmaceuticals Inc., a Carlsbad, California-based pioneer developer of RNA-targeted therapies, and Cleveland Clinic. First author Matthew Elitt worked in Tesars lab as a Case Western Reserve medical and graduate student.

PMD is a rare, genetic condition involving the brain and spinal cord that primarily affects boys. Symptoms can appear in early infancy and begin with jerky eye movements and abnormal head movements. Over time, children develop severe muscle weakness and stiffness, cognitive dysfunction, difficulty walking and fail to reach developmental milestones such as speaking. The disease cuts short life-expectancy, and people with the most severe cases die in childhood.

The disease results from errors in a gene called proteolipid protein 1 (PLP1). Normally, this gene produces proteolipid protein (PLP) a major component of myelin, which wraps and insulates nerve fibers to allow proper transmission of electrical signals in the nervous system. But a faulty PLP1 gene produces toxic proteins that kill myelin producing cells and prevent myelin from developing and functioning properly-resulting in the severe neurological dysfunction in PMD patients.

PMD impacts a few thousand people around the world. So far, no therapy has lessened symptoms or extended lifespans.

For nearly a decade, Tesar and his team have worked to better understand and develop new therapies for myelin disorders. They have had a series of successes, and their myelin-regenerating drugs for MS are now in commercial development.

In the current laboratory work, the researchers found that suppressing mutant PLP1 and its toxic protein restored myelin-producing cells, produced functioning myelin, reduced disease symptoms and extended lifespans.

After validating that PLP1 was their therapeutic target, the researchers pursued pre-clinical treatment options. They knew mutations in the PLP1 gene produced faulty RNA strands that, in turn, created the toxic PLP protein.

Additional team members included Lilianne Barbar, Elizabeth Shick, Yuka Maeno-Hikichi, Mayur Madhavan, Kevin Allan, Baraa Nawash, Artur Gevorgyan, Stevephen Hung, Zachary Nevin, Hannah Olsen, Daniela Schlatzer, David LePage, Weihong Jiang and Ronald Conlon from Case Western Reserve University School of Medicine; Berit Powers, Hien Zhao, Adam Swayze and Frank Rigo from Ionis Pharmaceuticals; and Midori Hitomi from Cleveland Clinic.

This research was supported by grants from the National Institutes of Health, New York Stem Cell Foundation and European Leukodystrophy Association. Philanthropic support was provided by the Geller, Goodman, Fakhouri, Long, Matreyak, Peterson and Weidenthal families and the CWRU Research Institute for Childrens Health.

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Case Western Reserve University-led team develops new approach to treat certain neurological diseases - Mirage News