Monthly Archives: June 2021

Engine Biosciences is a Singapore- and San Francisco-based company combining machine learning and genomics to decipher complex biology and uncover novel drugs and targets for areas of high unmet need. The venture-backed biotech received $10m in seed funding in 2018, and last week announced it had raised $43m in a series A round to fund the development of its NetMAPPR and CombiGEM technologies.

NetMAPPR is a searchable biology platform, which uses advanced computational tools to analyse large patient disease datasets. It can assess millions-to-billions of gene interactions to generate promising gene combinations and drug targets for specific patient populations.

The companys patented CombiGEM technology tests hundreds of thousands of gene interactions experimentally in diseased cells. The resulting data improves Engines machine learning algorithms, while high-ranking genes are prioritised for drug discovery and development.

Leveraging chemistry, artificial intelligence, combinatorial genetics and data science, Engines technologies enable researchers and drug developers to uncover the gene interactions and biological networks underlying diseases faster and more cost-effectively than conventional methods.

The companys growing pipeline of novel drugs for genetically defined patient populations has shown promise in treating liver, ovarian, colorectal and breast cancers, which represent approximately 2.5 million deaths every year in total. Engine is already progressing its novel biology findings into drug discovery programmes and proprietary small molecule inhibitors, and is exploring other disease areas through a series of collaborations.

The series A funding round was led by Polaris Partners and included several existing investors. The new funds will be used to expand Engines portfolio of precision oncology therapeutics, prepare for its first clinical programmes and scale its proprietary technology platform. Amy Schulman, managing partner at Polaris Partners, has also joined the Engine Biosciences Board of Directors.

Engine co-founder and CEO Jeffrey Lu said in a statement: Many breakthrough tools to edit, programme and modulate biology have emerged and matured in recent years. The fundamental question continues to be whether we know the disease-driving errors in the genetic code of biology to direct these tools, including therapeutics.

We are honoured that this preeminent group of life science and technology investors has recognised the progress our team has made and is supporting our mission to unleash new medicines by deciphering biology.

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Regenerative medicine: moving next-gen treatments from lab to clinic - Pharmaceutical Technology

NIH researchers discovered a new form of ALS that begins in childhood. The study linked the disease to a gene called SPLTC1. As part of the study, NIH senior scientist Carsten Bonnemann, M.D., (right) examined Claudia Digregorio (left), a patient from the Apulia region of Italy. Credit: Courtesy of the NIH/NINDS

NIH- and USU- led study links ALS to a fat manufacturing gene and maps out a genetic therapy.

In a study of 11 medical-mystery patients, an international team of researchers led by scientists at the National Institutes of Health and the Uniformed Services University (USU) discovered a new and unique form of amyotrophic lateral sclerosis (ALS). Unlike most cases of ALS, the disease began attacking these patients during childhood, worsened more slowly than usual, and was linked to a gene, called SPTLC1, that is part of the bodys fat production system. Preliminary results suggested that genetically silencing SPTLC1 activity would be an effective strategy for combating this type of ALS.

ALS is a paralyzing and often fatal disease that usually affects middle-aged people. We found that a genetic form of the disease can also threaten children. Our results show for the first time that ALS can be caused by changes in the way the body metabolizes lipids, said Carsten Bnnemann, M.D., senior investigator at the NIHs National Institute of Neurological Disorders and Stroke (NINDS) and a senior author of the study published inNature Medicine.We hope these results will help doctors recognize this new form of ALS and lead to the development of treatments that will improve the lives of these children and young adults. We also hope that our results may provide new clues to understanding and treating other forms of the disease.

Dr. Bnnemann leads a team of researchers that uses advanced genetic techniques to solve some of the most mysterious childhood neurological disorders around the world. In this study, the team discovered that 11 of these cases had ALS that was linked to variations in the DNA sequence of SPLTC1, a gene responsible for manufacturing a diverse class of fats called sphingolipids.

In addition, the team worked with scientists in labs led by Teresa M. Dunn, Ph.D., professor and chair at USU, and Thorsten Hornemann, Ph.D., at the University of Zurich in Switzerland. Together they not only found clues as to how variations in the SPLTC1 gene lead to ALS but also developed a strategy for counteracting these problems.

The study began with Claudia Digregorio, a young woman from the Apulia region of Italy. Her case had been so vexing that Pope Francis imparted an in-person blessing on her at the Vatican before she left for the United States to be examined by Dr. Bnnemanns team at the NIHs Clinical Center.

Like many of the other patients, Claudia needed a wheelchair to move around and a surgically implanted tracheostomy tube to help with breathing. Neurological examinations by the team revealed that she and the others had many of the hallmarks of ALS, including severely weakened or paralyzed muscles. In addition, some patients muscles showed signs of atrophy when examined under a microscope or with non-invasive scanners.

Nevertheless, this form of ALS appeared to be different. Most patients are diagnosed with ALS around 50 to 60 years of age. The disease then worsens so rapidly that patients typically die within three to five years of diagnosis. In contrast, initial symptoms, like toe walking and spasticity, appeared in these patients around four years of age. Moreover, by the end of the study, the patients had lived anywhere from five to 20 years longer.

These young patients had many of the upper and lower motor neuron problems that are indicative of ALS, said Payam Mohassel, M.D., an NIH clinical research fellow and the lead author of the study. What made these cases unique was the early age of onset and the slower progression of symptoms. This made us wonder what was underlying this distinct form of ALS.

The first clues came from analyzing the DNA of the patients. The researchers used next-generation genetic tools to read the patients exomes, the sequences of DNA that hold the instructions for making proteins. They found that the patients had conspicuous changes in the same narrow portion of the SPLTC1 gene. Four of the patients inherited these changes from a parent. Meanwhile, the other six cases appeared to be the result of what scientist call de novo mutations in the gene. These types of mutations can spontaneously occur as cells rapidly multiply before or shortly after conception.

Mutations in SPLTC1 are also known to cause a different neurological disorder called hereditary sensory and autonomic neuropathy type 1 (HSAN1). The SPLTC1 protein is a subunit of an enzyme, called SPT, which catalyzes the first of several reactions needed to make sphingolipids. HSAN1 mutations cause the enzyme to produce atypical and harmful versions of sphingolipids.

At first, the team thought the ALS-causing mutations they discovered may produce similar problems. However, blood tests from the patients showed no signs of the harmful sphingolipids.

At that point, we felt like we had hit a roadblock. We could not fully understand how the mutations seen in the ALS patients did not show the abnormalities expected from what was known about SPTLC1 mutations, said Dr. Bnnemann. Fortunately, Dr. Dunns team had some ideas.

For decades Dr. Dunns team had studied the role of sphingolipids in health and disease. With the help of the Dunn team, the researchers reexamined blood samples from the ALS patients and discovered that the levels of typical sphingolipids were abnormally high. This suggested that the ALS mutations enhanced SPT activity.

Similar results were seen when the researchers programmed neurons grown in petri dishes to carry the ALS-causing mutations in SPLTC1. The mutant carrying neurons produced higher levels of typical sphingolipids than control cells. This difference was enhanced when the neurons were fed the amino acid serine, a key ingredient in the SPT reaction.

Previous studies have suggested that serine supplementation may be an effective treatment for HSAN1. Based on their results, the authors of this study recommended avoiding serine supplementation when treating the ALS patients.

Next, Dr. Dunns team performed a series of experiments which showed that the ALS-causing mutations prevent another protein called ORMDL from inhibiting SPT activity.

Our results suggest that these ALS patients are essentially living without a brake on SPT activity. SPT is controlled by a feedback loop. When sphingolipid levels are high then ORMDL proteins bind to and slow down SPT. The mutations these patients carry essentially short circuit this feedback loop, said Dr. Dunn. We thought that restoring this brake may be a good strategy for treating this type of ALS.

To test this idea, the Bnnemann team created small interfering strands of RNA designed to turn off the mutant SPLTC1 genes found in the patients. Experiments on the patients skin cells showed that these RNA strands both reduced the levels of SPLTC1 gene activity and restored sphingosine levels to normal.

These preliminary results suggest that we may be able to use a precision gene silencing strategy to treat patients with this type of ALS. In addition, we are also exploring other ways to step on the brake that slows SPT activity, said Dr. Bonnemann. Our ultimate goal is to translate these ideas into effective treatments for our patients who currently have no therapeutic options.

Reference: Childhood Amyotrophic Lateral Sclerosis Caused by Excess Sphingolipid Synthesis by Mohassel, P. et al., 31 May 2021, Nature Medicine.DOI: 10.1038/s41591-021-01346-1

This study was supported by the NIH Intramural Research Program at the NINDS; NIH grants (NS10762, NS072446); the U.S. Department of Defenses Congressionally Directed Medical Research Programs (W81XWH-20-1-0219); the Swiss National Foundation (31003A_179371); the Deater foundation, Inc. The views expressed here do not represent those of the Department of Defense.

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Study of 11 Medical-Mystery Patients Results in Discovery of New Genetic Form of ALS in Children - SciTechDaily

DALLASMay 28, 2021A study of gene activity in the brains hippocampus, led by UT Southwestern researchers, has identified marked differences between the regions anterior and posterior portions. The findings, published today in Neuron, could shed light on a variety of brain disorders that involve the hippocampus and may eventually help lead to new, targeted treatments.

Genevieve Konopka, Ph.D.

These new data reveal molecular-level differences that allow us to view the anterior and posterior hippocampus in a whole new way, says study leader Genevieve Konopka, Ph.D., associate professor of neuroscience at UTSW.

She and study co-leader Bradley C. Lega, M.D., associate professor of neurological surgery, neurology, and psychiatry, explain that the human hippocampus is typically considered a uniform structure with key roles in memory, spatial navigation, and regulation of emotions. However, some research has suggested that the two ends of the hippocampus the anterior, which points downward toward the face, and the posterior, which points upward toward the back of the head take on different jobs.

Bradley C. Lega, M.D.

Scientists have speculated that the anterior hippocampus might be more important for emotion and mood, while the posterior hippocampus might be more important for cognition. However, says Konopka, a Jon Heighten Scholar in Autism Research, researchers had yet to explore whether differences in gene activity exist between these two halves.

For the study, Konopka and Lega, both members of the Peter ODonnell Jr. Brain Institute, and their colleagues isolated samples of both the anterior and posterior hippocampus from five patients who had the structure removed to treat epilepsy. Seizures often originate from the hippocampus, explains Lega, who performed the surgeries. Although brain abnormalities trigger these seizures, microscopic analysis suggested that the tissues used in this study were anatomically normal.

Marked differences in gene activity were identified in the anterior portion of the hippocampus, which points downward toward the face, and the posterior, which points upward toward the back of the head. Credit: Melissa Logies

After removal, the samples underwent single nuclei RNA sequencing (snRNA-seq), which assesses gene activity in individual cells. Although snRNA-seq showed mostly the same types of neurons and support cells reside in both sections of the hippocampus, activity of specific genes in excitatory neurons those that stimulate other neurons to fire varied significantly between the anterior and the posterior portions of the hippocampus. When the researchers compared this set of genes to a list of genes associated with psychiatric and neurological disorders, they found significant matches. Genes associated with mood disorders, such as major depressive disorder or bipolar disorder, tended to be more active in the anterior hippocampus; conversely, genes associated with cognitive disorders, such as autism spectrum disorder, tended to be more active in the posterior hippocampus.

Lega notes that the more researchers are able to appreciate these differences, the better theyll be able to understand disorders in which the hippocampus is involved.

The idea that the anterior and posterior hippocampus represent two distinct functional structures is not completely new, but its been underappreciated in clinical medicine, he says. When trying to understand disease processes, we have to keep that in mind.

Other UTSW researchers who contributed to this study include Fatma Ayhan, Ashwinikumar Kulkarni, Stefano Berto, Karthigayini Sivaprakasam, and Connor Douglas.

This work was funded by grants from the National Institutes of Health (NIH grants NS106447, T32DA007290, T32HL139438, NS107357), a University of Texas BRAIN Initiative seed grant (366582), the Chilton Foundation, the National Center for Advancing Translational Sciences of the NIH (under Center for Translational Medicine award UL1TR001105), the Chan Zuckerberg Initiative (an advised fund of the Silicon Valley Community Foundation, HCA-A-1704-01747), and the James S. McDonnell Foundation 21st Century Science Initiative in Understanding Human Cognition (scholar award 220020467).

About UTSouthwestern Medical Center

UTSouthwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institutions faculty has received six Nobel Prizes, and includes 25 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UTSouthwestern physicians provide care in about 80 specialties to more than 117,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 3 million outpatient visits a year.

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Same Difference: Two halves of the hippocampus have different gene activity - UT Southwestern

A massive genome-wide association study (GWAS) of genetic and health records of 1.2 million people from four separate data banks has identified 178 gene variants linked to major depression, a disorder that will affect one of every five people during their lifetimes.

The results of the study, led by the U.S. Department of Veterans Affairs (V.A.) researchers at Yale University School of Medicine and University of California-San Diego (UCSD), may one day help identify people most at risk of depression and related psychiatric disorders and help doctors prescribe drugs best suited to treat the disorder.

The study was published May 27 in the journal Nature Neuroscience.

For the study, the research team analyzed medical records and genomes collected from more than 300,000 participants in the V.A.s Million Veteran Program (MVP), one of the largest and most diverse databanks of genetic and medical information in the world.

These new data were combined in a meta-analysis with genetic and health records from the UK Biobank, FinnGen (a Finland-based biobank), and results from the consumer genetics company 23andMe. This part of the study included 1.2 million participants. The researchers crosschecked their findings from that analysis with an entirely separate sample of 1.3 million volunteers from 23andMe customers.

When the two sets of data from the different sources were compared, genetic variants linked to depression replicated with statistical significance for most of the markers tested.

Replication is a hallmark of good science, and this paper points to just how reliable and stable results from GWAS studies are becoming.

Daniel Levey

What is most heartening is we could replicate our findings in independent data sets, said Daniel Levey, an associate research scientist in the Yale Department of Psychiatry and co-lead author. Replication is a hallmark of good science, and this paper points to just how reliable and stable results from GWAS studies are becoming.

Like many mental health disorders, depression is genetically complex and is characterized by combinations of many different genetic variants, the researchers say.

Thats why we werent surprised by how many variants we found, said Joel Gelernter, the Foundations Fund Professor of Psychiatry at Yale, professor of genetics and of neuroscience, and co-senior author of the study. And we dont know how many more there are left to discover hundreds? Maybe even thousands?

The size of the new GWAS study will help clinicians to develop polygenic risk scores to pinpoint those most at risk of developing major depression and other related psychiatric disorders such as anxiety or post-traumatic stress disorder, the authors say.

The study also provides deep insights into the underlying biology of genetic disorders. For instance, one gene variant implicated in depression, NEGR1, is a neural growth regulator active in the hypothalamus, an area of the brain previously linked to depression. That confirms research done by the late Yale neuroscientist Ronald Duman on the role of neurotrophic factors in depression, Levey said.

Its really striking when completely different kinds of research converge on similar biology, and thats whats happening here, he said.

Insights into the functions of the variants can also help identify many drugs that hold promise in the treatment of depression, the researchers say. For instance, the drug riluzole, which is approved for the treatment of amyotrophic lateral sclerosis (ALS), modulates glutamate transmission in brain. Several gene variants linked by the new study to depression affect the glutamate system, which is actively being studied for depression treatments.

One of the real goals of the research is bringing forward new ways to treat people suffering from depression, added co-senior author Dr. Murray Stein, staff psychiatrist at the V.A. San Diego Healthcare System and Distinguished Professor of Psychiatry and Public Health at UCSD.

Research was primarily funded by the U.S. Department of Veterans Affairs, including the Million Veteran Program and the Cooperative Studies Program. Levey also received support from a NARSAD Young Investigator Award from the Brain & Behavior Research Foundation.

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Roots of major depression revealed in all its genetic complexity - Yale News

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. NAFLD patients are at higher risk of developing Non-alcoholic steatohepatitis (NASH), which causes severe and chronic liver inflammation, fibrosis and liver damage. A patient with NASH is believed to be at high risk for developing a form of liver cancer called hepatocellular carcinoma (HCC).

Apart from lifestyle interventions, there are currently no approved treatments for NASH. A liver transplant is sometimes the only remedy.

While risk factors for NASH (obesity, type-2 diabetes and gene mutations like PNPLA3) and HCC (Hepatitis B and C infections, alcohol overconsumption and cirrhosis) are well known, the precise mechanism of how simple fatty liver progresses to chronic inflammation, liver fibrosis, NASH and HCC is not known.

Debanjan Dhar, PhD, is co-senior author of the study and assistant professor in the Department of Medicine, Division of Gastroenterology at UC San Diego School of Medicine.

A recent study led by researchers at University of California San Diego School of Medicine found in a mouse model that when fed a Western diet rich in calories, fat and cholesterol, the mice progressively became obese, diabetic and developed NASH, which progressed to HCC, chronic kidney and cardiovascular disease.

The findings, published in the May 31, 2021 online edition of Cellular and Molecular Gastroenterology and Hepatology, showed that by simply changing the Western diet in a mouse model to a normal chow diet, where calories are derived from proteins and carbohydrates rather than fats, with no cholesterol, NASH and liver fibrosis were improved; and cancer progression and mortality prevented.

While the mice that continued on a Western diet developed HCC and had an increased risk of death, 100 percent of the mice that stopped the diet survived the length of the study without developing HCC, said Debanjan Dhar, PhD, co-senior author of the study and assistant professor in the Department of Medicine, Division of Gastroenterology at UC San Diego School of Medicine.

David Brenner, MD, is co-senior author and vice chancellor of UC San Diego Health Sciences.

This indicates that NASH and HCC may be a preventable disease and that diet plays a crucial role in the disease outcome.

In mice no longer fed the Western diet, researchers also found a decrease in liver fat and improvement in glucose tolerance an indicator of diabetes and several genes and cytokines that were affected in NASH returned to normal levels and function. In addition, Dhar and his team found key changes in the gut microbiome that modulate liver disease progression.

Although NASH is a liver disease, our results show its development and progression is orchestrated by multiple organs.

A surprising finding, said the researchers, was that when they switched the Western diet of the mice with NASH to normal chow, the effect was more pronounced on the liver rather than on whole body weight.

This could mean that slight changes in the liver might have profound effects on the disease outcome, said David Brenner, MD, co-senior author and vice chancellor of UC San Diego Health Sciences.

Researchers also compared mouse model findings to human patient datasets, indicating that gene expression changes in mouse livers were similar to human counterparts.

Our animal model provides an important pre-clinical testing platform to study the safety and efficacy of drugs that are currently being developed, as well as to test the repurposing of other drugs that are already FDA approved for other diseases, said Dhar.

Co-authors include: Souradipta Ganguly, Linshan Shang, Ruoyu Wang, Yanhan Wang, Bernd Schnabl, Rob Knight, Sara Brin Rosenthal, Gibraan Rahman, Anthony Diomino, Tatiana Kisseleva, Mojgan Hosseini and Mojgan Hosseini, all with UC San Diego; German Aleman Muench and Pejman Soorosh with Janssen Research and Development; and Hyeok Choon Kwon with National Medical Center, South Korea.

The research was funded, in part, by the National Institutes of Health (Grants DK120515, KL2TR001444 and 5P50AA011999), an ALF Liver Scholar award, the Southern California Research Center for ALPD and Cirrhosis.

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Diet Plays Critical Role in NASH Progressing to Liver Cancer in Mouse Model - UC San Diego Health

PARIS--(BUSINESS WIRE)--Regulatory News:

GenSight Biologics (Paris:SIGHT) (Euronext: SIGHT, ISIN: FR0013183985, PEA-PME eligible), a biopharma company focused on developing and commercializing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders, today announced that it will host a Key Opinion Leader (KOL) call on June 4, 2021 from 8:00 am to 9:00 am EDT. The webinar will feature presentations by KOLs Jos-Alain Sahel, MD (University of Pittsburgh School of Medicine) and Botond Roska, MD, PhD (Institute of Molecular and Clinical Ophthalmology Basel), who will discuss the Nature Medicine Case Report of partial recovery of visual function in a blind patient with late-stage retinitis pigmentosa (RP)., The subject is a participant in the ongoing PIONEER Phase I/II clinical trial of GenSight Biologics GS030 optogenetic therapy. Following the formal presentations, Drs. Sahel and Roska will be available to answer questions.

In addition, GenSight's management team will discuss highlights from the Nature Medicine Case Report and provide an update on their pipeline candidate, GS030. Administered via intravitreal injection, GS030 uses an optimized viral vector (GS030-DP) to express the light-sensitive opsin ChrimsonR in retinal ganglion cells and proprietary light-stimulating goggles (GS030-MD) to project the right wavelength and intensity of light onto the treated retina.

The webinar will be webcast live at https://bit.ly/3uzvG1j. You will need to register in advance to get access to the webinar. For those unable to attend the live broadcast, a recording will be accessible using the same link.

The Nature Medicine Case Report can be found at https://www.nature.com/articles/s41591-021-01351-4. A video of the patient performing the tests, which was submitted as supplementary material to the publication, can be viewed at http://www.gensight-biologics.com.

About GenSight Biologics

GenSight Biologics S.A. is a clinical-stage biopharma company focused on developing and commercializing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders. GenSight Biologics pipeline leverages two core technology platforms, the Mitochondrial Targeting Sequence (MTS) and optogenetics, to help preserve or restore vision in patients suffering from blinding retinal diseases. Using its gene therapy-based approach, GenSight Biologics product candidates are designed to be administered in a single treatment to each eye by intravitreal injection to offer patients a sustainable functional visual recovery. Developed as a treatment for Leber Hereditary Optic Neuropathy (LHON), GenSight Biologics lead product candidate, LUMEVOQ (GS010; lenadogene nolparvovec), is currently in the review phase of its registration process in Europe, and in Phase III to move forward to a BLA filing in the U.S.

About GS030

GS030 leverages GenSight Biololgics optogenetics technology platform, a novel approach to restore vision in blind patients using a combination of ocular gene therapy and tailored light-activation of treated retinal cells. The gene therapy, which is delivered via a single intravitreal injection, introduces a gene encoding for a light-sensitive protein (ChrimsonR-tdT) into retinal ganglion cells, making them responsive to light and bypassing photoreceptors killed off by diseases such as retinitis pigmentosa (RP). Because ChrimsonR-tdT is activated by high intensities of amber light, a wearable medical device is needed to stimulate the treated retina. The optronic light-stimulating goggles (GS030-MD) encode the visual scene in real-time and project a light beam with a specific wavelength and intensity onto the treated retina. Treatment with GS030 requires patients to wear the external wearable device in order to enable restoration of their visual function. With the support of the Institut de la Vision in Paris and the team of Dr. Botond Roska at the Friedrich Miescher Institute in Basel, GenSight is investigating GS030 as therapy to restore vision in patients suffering from late-stage RP. GenSights optogenetics approach is independent of the specific genetic mutations causing blindness and has potential applications in other diseases of the retina in which photoreceptors degenerate, like dry age-related macular degeneration (dry-AMD). GS030 has been granted Orphan Drug Designation in the United States and Europe.

About Optogenetics

Optogenetics is a biological technique that involves the transfer of a gene encoding for a light sensitive protein to cause neuronal cells to respond to light stimulation. As a neuromodulation method, it can be used to modify or control the activities of individual neurons in living tissue and even in-vivo, with a very high spatial and temporal resolution. Optogenetics combines (1) the use of gene therapy methods to transfer a gene into target neurons with (2) the use of optics and electronics (optronics) to deliver the light to the transduced cells. Optogenetics holds clinical promise in the field of vision impairment or degenerative neurological disorders.

About Retinitis Pigmentosa

Retinitis pigmentosa (RP) is a family of orphan genetic diseases caused by multiple mutations in numerous genes involved in the visual cycle. Over 100 genetic defects have been implicated. RP patients generally begin experiencing vision loss in their young adult years, with progression to blindness by age 40. RP is the most widespread hereditary cause of blindness in developed nations, with a prevalence of about 1.5 million people throughout the world. In Europe and the United States, about 350,000 to 400,000 patients suffer from RP, and every year between 15,000 and 20,000 new patients with RP lose sight. There is currently no curative treatment for RP.

About the PIONEER Phase I/II trial

PIONEER is a first-in-man, multi-center, open label dose-escalation study to evaluate the safety and tolerability of GS030 in 12-18 subjects with late-stage retinitis pigmentosa. GS030 combines a gene therapy (GS030-DP) administered via a single intravitreal injection with a wearable optronic visual stimulation device (GS030-MD). Eligible patients in the first three cohorts are those affected by end-stage non-syndromic RP with no light perception (NLP) or light perception (LP) levels of visual acuity. The extension cohort will include patients with hand motion (HM) and counting fingers (CF) levels of visual acuity.

As per protocol, three cohorts with three subjects each will be administered an increasing dose of GS030-DP via a single intravitreal injection in their worse-seeing eye. An extension cohort will receive the highest tolerated dose. The DSMB will review the safety data of all treated subjects in each cohort and will make recommendations before a new cohort receives the next dose. The primary outcome analyses will be on the safety and tolerability at one year post-injection. PIONEER is being conducted in three centers in the United Kingdom, France and the United States.

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GenSight Biologics to Host a Key Opinion Leader Webinar on the Nature Medicine Case Report: Visual Recovery after GS030 Optogenetic Treatment -...

Key Highlights:

MELBOURNE, Australia, June 01, 2021 (GLOBE NEWSWIRE) -- Genetic Technologies Limited (ASX: GTG; NASDAQ: GENE, Company, GTG), a diversified Genomics and AI-driven preventative health business, is pleased to announce the official launch of its COVID-19 Serious Disease Risk Test (COVID-19 Risk Test) in the US through its partnership with Infinity BiologiX LLC (IBX). IBX will produce, distribute, and sell GENEs test across its established network, https://ibx.bio/services/covid-19-severity-test/

Designed to predict disease severity using genetic and clinical information the test provides a risk score to help individuals aged 18 years and over to understand their personal risk of contracting a serious case of COVID-19. In addition, employers, governments, and other public health entities may use the data to make informed decisions about disease risk, treatment options, and vaccination priorities. This will assist in guiding proactive steps to minimize disease exposure and manage the pandemic in the weeks and months ahead.

This is a fantastic milestone for our team, commented Simon Morriss, CEO of Genetic Technologies. Our COVID-19 Risk Test is a crucial product that will provide individuals with the ability to understand their personal risk associated with contracting a serious case of this disease. Alongside existing treatment options and vaccines, we believe this test will enable more insightful decisions for states, workplaces and individuals on pathways forward in managing this pandemic.

IBX is a market-disrupting central laboratory supporting academia, government, and industry. IBX provides global sample collection, processing, storage, and analytical services integrated with scientific and technical support in both the research and clinical arenas. As a leader in biomaterials, IBX provides support to the development of diagnostics, therapeutics, and research in the genomics, precision, and regenerative medicine arenas.

Extensive experience with large-scale COVID testing and sample processing made IBX a clear choice for this endeavor. Through its labs in New Jersey and Minnesota and with partner organizations around the US, the company is able to process over 100,000 risk tests per day.

IBX launched its COVID-19 saliva-test in May 2020, after receiving FDA Emergency Use Authorization. It was the first test to utilize saliva as the primary biomaterial for SARS-CoV-2, and IBX subsequently became the first company to offer an at-home collection with this approach.

Developed by GENE, the COVID-19 risk test will be distributed and sold in the US by IBX, released under GENEs powered by GeneType brand, and is applicable to men and women ages 18 and up. IBX will determine sales and end consumer pricing structure for the risk test and will produce, distribute, and market it in the US.

About Genetic Technologies Limited Genetic Technologies Limited (ASX: GTG; Nasdaq: GENE) is an Australian based diversified molecular diagnostics company. GENE offers cancer predictive testing and assessment tools to help physicians proactively manage patient health. The companys lead products, GeneType for Breast Cancer for non-hereditary breast cancer and GeneType for Colorectal Cancer, are clinically validated risk assessment tests and are first in class. Genetic Technologies is developing a pipeline of risk assessment products based on a world leading technology platform created over the past 10 years.

For more information, please visit http://www.genetype.com

About Infinity BiologiX LLC: Infinity BiologiX (IBX) is a market-disrupting central laboratory supporting academia, government, and industry. IBX provides global sample collection, processing, storage, and analytical services integrated with scientific and technical support in both the research and clinical arenas. As a leader in biomaterials, IBX provides support to the development of diagnostics, therapeutics, and research in the genomics, precision, and regenerative medicine arenas. IBX previously operated as RUCDR Infinite Biologics before spinning off from Rutgers University-New Brunswick in August 2020.

For more information, visit http://www.ibx.bio

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Genetic Technologies' COVID-19 Risk Test Now Available in US through Partnership with Infinity BiologiX - GlobeNewswire

HOUSTON and SAN DIEGO, June 1, 2021 /PRNewswire/ -- Neurophth Biotechnology Ltd., a fully-integrated genetic medicines company developing AAV-mediated gene therapies for the treatment of ocular diseases, and Hopstem Biotechnology, the leading human induced pluripotent stem cell (hiPSC) and neural differentiation technology platform company, today announced a strategic partnership aiming to provide human iPSC-derived cell therapy for ocular diseases.

The partnership leverages Neurophth's experience in global gene/cell therapy drugs development and understanding of ophthalmic diseases to complement Hopstem's expertise in GMP manufacturing and quality assurance of iPSC-derived clinical cell products to provide next-generation ocular treatments. Under the terms of agreement, Hopstem Biotechnology will receive upfront and milestone payments for the development of candidate cell product for agreed retinal degenerative disorder. Neurophth will have the option to license the candidate product and will be responsible for development and commercialization of the licensed product. In addition, Neurophth agreed to license Hopstem's iPSC reprogramming patent and GMP iPSC line with additional payments to Hopstem at different product development stages. According to the agreement, Hopstem will also share part of the product sales.

"This collaboration exemplifies Neurophth's long-term commitment to advancing the field of ophthalmic treatment as we continue to expand and progress our innovative pipeline of ocular candidates," said Bin Li, M.D., Ph.D., Founder and Chairman of Neurophth Therapeutics. "Combining the methods of stem cell technology, induced pluripotent stem cells is a promising technology that can offer an extraordinary potential for regenerative therapy, disease modeling and drug screening."

"We are very excited by this partnership with Neurophth. The human induced pluripotent stem cell (hiPSC) line we developed is made by transforming the skin of a healthy donor into stem cells that are capable of multiplying and becoming any type of cell in the human body, meeting GMP requirements. Thanks to our iPSC-derived clinical cell product manufactory and quality platform developed since 2019, we are able to speed up ocular cell product development with Neurophth, the leading ocular therapy company in the field. Together, our aim is to offer safe and effective regenerative medicine with hiPSC-derived cellsfor reversing the progression of ocular diseases and restoring vision for patients," Jing Fan, Ph.D., Founder and CEO of Hopstem Biotechnology.

"iPSCs holds the promise for treatment of retinal degenerative disorders where AAV-mediated gene therapy is unreachable," said Alvin Luk, Ph.D., M.B.A., CEO at Neurophth. "Hopstem is one of the most respected pioneers in the field of iPSC translational medicine. We are confident that their technology and expertise, combined with Neurophth's deep knowledge in ophthalmology and drug development, has the potential to unlock future generations of gene/cell therapy treatments for patients."

About Neurophth

Neurophth is China's first gene therapy company for ophthalmic diseases. Headquartered in Wuhan with subsidiaries in Shanghai, Suzhou, and US, Neurophth, a fully integrated company, is striving to discover and develop gene therapies for patients suffering from blindness and other eye diseases globally. Our validated AAV platform which has been published in Nature - Scientific Reports, Ophthalmology, and EBioMedicine, has successfully delivered proof-of-concept data with investigational gene therapies in the retina. Our most advanced investigational candidate, NR082 (NFS-01 project, rAAV2-ND4), in development for the treatment ofND4-mediated Leber hereditary optic neuropathy (LHON), has granted orphan designation by theU.S FDA and its IND has also been approved by China NMPA. The pipeline also includesND1-mediated LHON, autosomal dominant optic atrophy, optic neuroprotection (e.g., glaucoma), vascular retinopathy (e.g., diabetic macular edema and wet age-related macular degeneration), and five other preclinical candidates. Neurophth has initiated the scaling up in-house manufacturing process in single-use technologies to support future commercial demand at the Suzhou facility. To learn more about us and our growing pipeline, please visitwww.neurophth.com.

About Hopstem

Hopstem Biotechnology is one of the first few iPSC cell therapy companies in China. The company was founded in January 2017 in Hangzhou (China) and Baltimore (US) by neuroscientists and stem-cell biologists from Johns Hopkins University. Hopstem has established a world-leading neural differentiation platform as well as patented iPSC reprogramming method and high standard GMP manufactory and quality system. The mission of Hopstem is to apply these cutting-edge technologies to develop innovative cell therapies for CNS and other disorders. Our leading clinical product, hNPC01, is a human forebrain neural progenitor cell product for stroke and traumatic brain injuries, etc. Preliminary studies in rat and monkey pMCAO stroke models have suggested that majority of those transplanted hNPCs differentiated into functional neural cells and formed significant new connections with the rat neurons in distal regions. To learn more about us, please visit http://www.hopstem.com.

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SOURCE Neurophth Therapeutics, Inc.

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Neurophth Therapeutics and Hopstem Biotechnology Announce Strategic Partnership to Develop Human Induced Pluripotent Stem Cell-Derived Therapies for...

On May 17, NHGRI announced plans to appoint Vence Bonham Jr., J.D. as acting deputy director. Vence, who joined NHGRI in 2003, is currently senior advisor to the NHGRI director on genomics and health disparities as well as head of the Health Disparities Unit in NHGRIs Social and Behavioral Research Branch. His appointment as acting deputy director will expand on his current roles, in which he has made major contributions to the Institutes research on diversity, inclusion, and health equity. In this new role, Vence will assume a more elevated position at the Institute, helping the NHGRI leadership advance NHGRIs mission and priorities.

The NHGRI deputy director position has been vacant since Mark Guyer, Ph.D., retired in 2014. The upcoming appointment of Vence as the NHGRI acting deputy director reflects the Institutes desire to have a leader at the highest possible level to guide programmatic activities to advance work related to diversity, inclusion, and health equity at the national level, but also lead NIH and NHGRIs efforts to address anti-racism and social justice. These are significant priority areas for NHGRI, and Vences leadership will be invaluable.

One of Vences first responsibilities as acting deputy director will be to create a new Office of Workforce Diversity and Health Equity within the NHGRI Office of the Director. The new office will work towards NHGRIs goals Vence will work closely with other NHGRI leaders to develop the offices mission and vision, establish a staffing plan, and lead efforts to recruit its first director.

Vence is familiar with NHGRIs long-standing leadership on issues related to diversity in genomics. Most recently, he led the NHGRI Genomic Workforce Diversity Working Group that established an action agenda for enhancing the diversity of the genomics workforce, which was published earlier this year. Vence and NHGRIs Director, Dr. Eric Green, also co-authored a commentary in the American Journal of Human Genetics, which described the imperative to enhance the diversity of the genomics workforce for achieving the promise of genomics. In his new role, Vence will focus on implementing this action agenda and will continue to be one of three NHGRI leaders serving on key NIH-wide committees as part of the NIH UNITE Initiative, which aims to end structural racism in biomedical research.

Vence also has a long history of starting successful initiatives at NHGRI. He established the Education and Community Involvement Branch and served as its inaugural chief. The branch thrived under his leadership, including the creation of the Smithsonian-NHGRI exhibition, Genome: Unlocking Lifes Code.

His research program focuses primarily on the social implications of new scientific knowledge, particularly in communities of color. He and his group study how genomics influences the use of the constructs of race and ethnicity in biomedical research and clinical care, as well as how genomics worsens or improves health inequities. They also study sickle cell disease, a condition that is affected by emerging curative genomic technologies and that faces significant health disparities both in the US and worldwide.

Vences appointment as the NHGRI acting deputy director is anticipated to begin in early summer.

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Vence Bonham to be appointed acting NHGRI deputy director - National Human Genome Research Institute

Many of us are familiar with Parkinsons disease, but the term parkinsonism may not be as familiar.

Parkinsonism is a term for a group of neurological conditions that cause difficulty with movement. Some of the defining symptoms of parkinsonism include:

Parkinsons disease is the most common type of parkinsonism. It makes up about 80 percent of parkinsonism cases.

Other types of parkinsonism are collectively known as atypical parkinsonian disorders or Parkinson-plus syndromes. There are many types of parkinsonism that closely mimic symptoms of Parkinsons, and diagnosis can be difficult.

In this article, we look at the different types of parkinsonism and break down the symptoms and treatment of each.

Parkinsons disease is one of many types of parkinsonism. Its caused by a loss of cells in the part of your brain that produces the neurotransmitter dopamine.

Parkinsons disease and the different types of parkinsonism progress in different ways. Some may progress more rapidly than Parkinsons disease. Others, like secondary parkinsonism, may be reversible.

The conditions also respond differently to treatments. For instance, someone who has a type of parkinsonism may not respond to the drug levodopa, which is commonly used for Parkinsons disease.

It can be hard to tell the difference between types of parkinsonism. Heres a look at some of the identified categories of parkinsonism with their typical symptoms and treatments.

Atypical parkinsonism refers to any type of parkinsonism that isnt Parkinsons disease.

Types of atypical parkinsonism include:

Multiple system atrophy is a rare and progressive disease thats characterized by abnormal deposits of protein in the nervous system. The cause is unknown, and it affects about 15,000 to 50,000 Americans.

The initial symptoms are similar to those of Parkinsons disease, but they tend to progress more quickly. They include:

Theres currently no treatment for multiple system atrophy thats known to delay the progression of the disease. Treatment involves targeting individual symptoms.

Progressive supranuclear palsy is a disorder caused by damage to parts of the brain controlling the cranial nerves. Symptoms vary between people, but the first sign is often loss of balance while walking. This condition also progresses faster than Parkinsons disease.

Other signs include:

Theres no effective treatment for progressive supranuclear palsy, and it usually doesnt respond to medication. Treatment revolves around targeting individual symptoms.

Corticobasal syndrome is a progressive neurological disorder that leads to the deterioration of certain areas of your brain. The initial sign is often trouble moving one limb. Eventually, this movement difficulty spreads to all limbs.

The onset of this syndrome is usually between ages 50 to 70. It affects roughly 5 in 100,000 people.

Symptoms vary greatly but may include:

No treatment has been found to slow the progression of corticobasal syndrome. Parkinsons drugs are generally ineffective but may help manage stiffness in some people.

Dementia with Lewy bodies is a disease that leads to deposits of alpha-synuclein proteins in the brain. These proteins are also called Lewy bodies.

Abnormal build-up of these chemicals can cause movement, behavior, mood, and cognitive changes.

More than 1 million people in the United States have Lewy body dementia. It most often occurs in adults over 50 and can progress for 2 to 20 years from its onset to death.

Movement symptoms include:

Cognitive symptoms can include:

Secondary parkinsonism is when a medical condition or medication leads to symptoms that resemble Parkinsons. The most common cause of secondary parkinsonism is a side effect of medications, also known as pseudoparkinsonism.

Some drugs can interfere with dopamine transmission in your brain and cause symptoms resembling Parkinsons.

Drugs that are known to induce parkinsonism include:

Treatment usually involves lowering the dose or ceasing use of the offending medication.

A number of underlying conditions can potentially lead to brain damage that causes parkinsonism. Some conditions include:

Treatment for parkinsonism caused by an underlying condition involves targeting the root cause and treating the symptoms.

Its thought that multiple small strokes in the part of your brain that controls movement can lead to a condition called vascular parkinsonism. Vascular parkinsonism is characterized by parkinsonism symptoms primarily in the lower limbs and an unsteady gait in the absence of tremors.

Symptoms include:

Vascular parkinsonism is typically poorly responsive to the medication levodopa. Treatment primarily focuses on treating symptoms. Physical therapy and lifestyle changes to improve cardiovascular health are often recommended.

Infantile parkinsonism-dystonia is a rare disorder thats also known as dopamine transporter deficiency syndrome. It causes a progressive decline in involuntary muscle contractions and other symptoms that resemble those of Parkinsons disease. It usually begins in infants.

Theres no cure for infantile parkinsonism-dystonia, and its caused by a mutation of the gene SLC6A3.

Symptoms of infantile parkinsonism-dystonia include:

Other symptoms can be present, like:

Treatment involves targeting individual symptoms to increase quality of life. Medications to control involuntary muscular contractions and physical therapy are also commonly used.

Juvenile parkinsonism develops before the age of 21. Juvenile parkinsonism that responds to the medication levodopa is most often caused by mutations in the genes PARK-Parkin, PARK-PINK1, or PARK-DJ1.

The symptoms of juvenile parkinsonism are the same as late-onset parkinsonism, but the onset is at a younger age.

The medication levodopa is the most common treatment. But other supportive therapies may also be used, like botulinum toxin for treating involuntary spasms, as well as deep brain stimulation and physical therapy.

No single test can diagnose parkinsonism disorders. Doctors use a combination of tests to rule out other possible conditions and make a diagnosis based on your symptoms and medical history.

For many types of parkinsonism, the exact cause isnt known. Genetic and environmental factors are both believed to play a role.

Parkinsons disease has been linked to exposure to pesticides and herbicides, as well as living close to industrial plants. Some genes are also associated with an elevated risk of developing Parkinsons.

Conditions that cause brain damage, like traumatic injuries, tumors, and exposure to certain toxins, are also potentially contributing factors to the development of parkinsonism.

The outlook of parkinsonism is highly variable depending on factors like the age of onset, the underlying cause, and your overall health. For example, late-onset Parkinsons disease tends to progress faster and cause earlier cognitive dysfunction than early-onset Parkinsons.

Parkinsonisms are progressive conditions that get worse over time. Initiating treatment shortly after symptoms begin can help increase life expectancy and improve quality of life.

For Parkinsons, the primary treatment is the medication levodopa. Treatment varies for other types of parkinsonism, but primarily involves managing symptoms.

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Parkinsonism: Types, Causes, and More - Healthline