Category Archives: Gene Medicine

Scientist in Baltimore has discovered a catfish gene that, when activated in a rodent brain, can sense electromagnetic fields. There are numerous animals, throughout all types and species, expect humans (supposedly), that can sense the feeble network of Earths electromagnetic global field. The glass catfish is one of those animals and Galit Pelled, the lead researcher and associate professor at John Hopkins University School of Medicine and Kennedy Kreiger Institute, plus his team are hoping its electromagnetic perceptive gene (EPG) will one day be used to manipulate heart and brain cells. This non-evasive wireless technique of controlling human cells could replace pacemakers, treat epilepsy, or even help create an interface between the human brain and a machine.

Previously, researchers discovered similar genes in bacteria and birds but those created a chemical compound responsible for sensing the magnetic fields. This recent discovery, which was presented by Pelled at the 2017 International IEEE EMBS Conference on Neural Engineering, is different since the gene works alone for function and is, therefore, simpler to manipulate.

By injecting different strands of the catfish gene into frog eggs, Pelled and his lab mates were eventually able to discover which eggs responded to magnets and which bits of DNA were responsible for the electromagnetic perception.

While Assaf Gilad, co-author of the study and an associate professor of radiology at Johns Hopkins Medicine, says We dont know exactly what the protein is doing, they do know the end result. The responsible protein adheres to a cell surface and then the cell is filled with calcium. In heart cells and neurons, a sudden flush of calcium turns the cell on, so it begins to beat or fire. By expressing the genes in a group of brain cells, and later, a living rat brain, the team of researchers could activate the neural cells with only an electromagnetic field and no other devices.

Currently, doctors are able to treat conditions such as epilepsy and depression, ailments related to misfiring neurons, using invasive deep brain stimulation. Gilad hopes that with EPGs, delivered by gene therapy or transplants, these illnesses could be eased through wireless manipulation instead. Similarly, electromagnetic genes have the likelihood to be useful for heart conditions too, replacing traditional pacemakers with a biological one made EPGs. The ability to remotely control neuronal activity is big, says Gilad. But its still in the early, experimental stages.

At the moment, researchers have only identified one part of the glass catfishs electromagnetic sensing abilities and their current focus is understanding the system in general with immediate medical applications as their goal.

More News to Read

comments

Read the original post:
Home Science Research Scientist Discovered a Catfish Gene, When activated in a Rodent Brain, Can... - TrendinTech

SUNDAY, June 4, 2017 (HealthDay News) -- A twice-daily pill could help some advanced breast cancer patients avoid or delay follow-up sessions of chemotherapy, a new clinical trial reports.

The drug olaparib (Lynparza) reduced the chances of cancer progression by about 42 percent in women with breast cancer linked to BRCA1 and BRCA2 gene mutations, according to the study.

Olaparib delayed cancer progression by about three months. The drug also caused tumors to shrink in three out of five patients who received the medication, the researchers reported.

"Clearly the drug was more effective than traditional chemotherapy," said Dr. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society.

"This is a group where a response is more difficult to obtain -- a young group with a more aggressive form of cancer -- and nonetheless we saw a close to 60 percent objective response rate," he said.

The study was funded by AstraZeneca, the maker of Lynparza.

Olaparib works by cutting off the avenues that malignant cancer cells use to stay alive, said lead researcher Dr. Mark Robson. He's a medical oncologist and clinic director of Clinical Genetics Service at Memorial Sloan Kettering Cancer Center in New York City.

The drug inhibits PARP, an enzyme that helps cells repair damaged DNA, Robson said.

Normal cells denied access to PARP will turn to the BRCA genes for help, since they also support the repair of damaged DNA, Robson said.

But that "backup capability" is not available to breast cancer cells in women with BRCA gene mutations, Robson said.

"When you inhibit PARP, the cell can't rescue itself," Robson said. "In theory, you should have a very targeted approach, one specifically directed at the cancers in people who have this particular inherited predisposition."

Olaparib already has been approved by the U.S. Food and Drug Administration for use in women with BRCA-related ovarian cancer. Robson and his colleagues figured that it also should be helpful in treating women with breast cancer linked to this genetic mutation.

The study included 302 patients who had breast cancer that had spread to other areas of their body (metastatic breast cancer). All of the women had an inherited BRCA mutation.

They were randomly assigned to either take olaparib twice a day or receive standard chemotherapy. All of the patients had received as many as two prior rounds of chemotherapy for their breast cancer. Women who had hormone receptor-positive cancer also had been given hormone therapy.

After 14 months of treatment, on average, people taking olaparib had a 42 percent lower risk of having their cancer progress compared with those who received another round of chemotherapy, Robson said.

The average time of cancer progression was about seven months with olaparib compared with 4.2 months with chemotherapy.

Tumors also shrank in about 60 percent of patients given olaparib. That compared with a 29 percent reduction for those on chemotherapy, the researchers said.

Severe side effects also were less common with olaparib. The drug's side effects bothered 37 percent of patients compared with half of those on chemo. The drug's most common side effects were nausea and anemia.

"There were fewer patients who discontinued treatment because of toxicity compared to those who received chemotherapy," Robson said. "Generally it was pretty well tolerated."

Only about 3 percent of breast cancers occur in people with BRCA1 and BRCA2 mutations, the researchers said in background notes.

Despite this, the results are "quite exciting," said Dr. Julie Fasano, an assistant professor of hematology and medical oncology at the Icahn School of Medicine at Mount Sinai in New York City.

Olaparib could wind up being used early in the treatment of metastatic breast cancer as an alternative to chemotherapy, and future studies might find that the drug is effective against other forms of breast cancer, Fasano said.

"It may be a practice-changing study, in terms of being able to postpone IV chemotherapy and its associated side effects" like hair loss and low white blood cell counts, Fasano said.

Lichtenfeld noted that olaparib also places less burden on patients.

"It may be easier for women to take two pills a day rather than go in for regular chemotherapy," Lichtenfeld said. "Clearly, this is a treatment that will garner considerable interest.

The findings were scheduled to be presented Sunday at the American Society of Clinical Oncology's annual meeting, in Chicago. The study was also published June 4 in the New England Journal of Medicine.

Read the original:
Drug Helps Fight Breast Tumors Tied to 'Cancer Genes' - The Tand D.com

An experimental cancer medicine called larotrectinib has shown promise in treating a diverse range of cancers in people young and old, researchers said at a major cancer conference in the United States.

The treatment targets a genetic abnormality which is often found in rare cancers including salivary gland cancer, juvenile breast cancer, and a soft tissue cancer known as infantile fibrosarcoma which are particularly difficult to treat. This abnormality also occurs in about 0.5% to 1% of many common cancers.

In the study released at the American Society of Clinical Oncology conference, 76% of cancer patients both children and adults with 17 different kinds of cancer responded well to the medicine.

A total of 79% were alive after one year. The study is ongoing. And 12% went into complete remission from their cancer.

The clinical trial included 55 patients 43 adults and 12 children. All had advanced cancers in various organs, including the colon, pancreas and lung, as well as melanoma.

These findings embody the original promise of precision oncology: treating a patient based on the type of mutation, regardless of where the cancer originated, said lead study author David Hyman, chief of early drug development at Memorial Sloan Kettering Cancer Center in New York.

We believe that the dramatic response of tumours with TRK fusions to larotrectinib supports widespread genetic testing in patients with advanced cancer to see if they have this abnormality.

Researchers said 76% of cancer patients both children and adults with 17 different kinds of cancer responded well to the medicine. (Shutterstock)

Made by Loxo Oncology Inc., larotrectinib is a selective inhibitor of tropomyosin receptor kinase (TRK) fusion proteins. TRK proteins are a product of a genetic abnormality when a TRK gene in a cancer cell fuses with one of many other genes, researchers said.

The US Food and Drug Administration has not yet approved the treatment for widespread use.

The treatment was well tolerated by patients, and the most common side effects were fatigue and mild dizziness.

If approved, larotrectinib could become the first therapy of any kind to be developed and approved simultaneously in adults and children, and the first targeted therapy to be indicated for a molecular definition of cancer that spans all traditionally-defined types of tumors. said Hyman.

Follow @htlifeandstyle for more

Visit link:
New cancer medicine targets rare genetic flaw, finds study - Hindustan Times

The founding mission of MIT may seem like an unusual meal-time story for a child. But when Mark Bathe was growing up, it was a regular topic of conversation around the dinner table.

That is because Bathes father, mechanical engineer Klaus-Jrgen Bathe, was a long-standing, proud MIT faculty member, and regularly talked about MIT founder William Barton Rogers mission for the Institute.

Bathes father was a huge presence in his childhood, and his enthusiastic descriptions of MITs focus on fundamental yet hands-on science to benefit society made quite an impression on him. My father was the lens through which I saw the world, Bathe says.

So when Bathe was admitted to both MIT and another university as a senior in high school, there was little doubt in his mind as to where he would be enrolling.

Bathe joined MITs Department of Mechanical Engineering as an undergraduate, where he considers himself fortunate to have been trained in a broad and fundamental, yet problem-oriented, manner.

But with a longstanding desire to impact human health through medicine, Bathe moved on to graduate research in biomechanical engineering, in part under the stewardship of Alan Grodzinsky, a professor of biological, mechanical, and electrical engineering, and director of the MIT Center for Biomedical Engineering.

After receiving his PhD in 2004, Bathe decided to deepen his understanding of biomolecules by moving to the University of Munich in 2006, to carry out postdoctoral research in biological physics.

He then returned to MIT in 2009, joining the Department of Biological Engineering, where he established an interdisciplinary research group focused on using approaches from engineering, chemistry, physics, and computer science to understand and solve problems in applied biology.

I find the new emerging world of personalized medicine fascinating, Bathe says. In particular, the prospect of using gene-editing tools to correct disease-causing mutations that are either inherited or acquired, as well as the use of messenger RNAs to express specific proteins that are needed to alleviate disease.

Bathe, now an associate professor of biological engineering at MIT, creates a huge variety of programmed three-dimensional shapes out of single strands of synthetic DNA, a process known as DNA origami. These nanoparticles may ultimately be deployed as structural scaffolds to deliver vaccines, drugs, or even gene-editing tools such as CRISPR-Cas9 to specific parts of the body, he says.

Once delivered, the therapeutic payload could be released to edit the faulty genes that cause certain diseases.

It amazes me that with two therapeutic tools, namely CRISPR for gene editing and therapeutic messenger RNAs for protein production, we could, in principle, cure nearly any disease, potentially with minimal side-effects, but only if we can figure out how to successfully deliver these tools to act highly specifically in the target cells of interest, such as the gut, lungs, brain, or other organs, he says.

Tackling this problem can only be achieved through an interdisciplinary, long-term research effort, he believes.

Targeted therapeutic delivery is a highly interdisciplinary problem, involving everything from very applied, clinical medicine to basic macromolecular chemistry of nucleic acids and proteins, as well as the physics and engineering of macromolecular transport, Bathe says.

As a starting point, his laboratory, which includes engineers, chemists, computer scientists, and physicists, developed DAEDALUS (DNA Origami Sequence Design Algorithm for User-defined Structures), an algorithm designed to automate the process of assembling DNA nanoparticles. DAEDALUS, which takes a simple 3-D representation of the object and determines how this should be assembled from the DNA strands, can build any type of enclosed 3-D shape.

As a result, the algorithm, combined with new nucleic acid synthesis procedures, which were published in a paper in the journal Science last year, are allowing Bathe and his team to build the nanoparticles far more quickly and easily than was previously possible.

Despite decades of research into the delivery of nucleic acids and proteins, and the considerable potential for these therapeutics in clinical medicine, little progress has been made as measured by FDA-approved therapies, says Bathe. This is likely due in part to our poor understanding of macromolecular transport in the complex human anatomy, but also due to the lack of techniques available to engineer delivery tools, he says.

Were hopeful that fully synthetic, viral-like nucleic acid nanoparticles developed in our lab offer a new opportunity for the rational engineering of delivery tools for gene-centric therapies, he explains.

Working with with the Stanley Center for Psychiatric Research, Bathe and his team are also investigating novel methods of imaging patient-derived neuronal cells, in a bid to better understand how genes affect the signals sent between individual neurons in the brain.

He is also investigating the use of DNA and other molecules to store and process information, with density that is orders of magnitude higher than conventional silicon-based computing hardware.

When not in the classroom or his laboratory, Bathe takes part in a range of outdoor activities, including cycling, running, skiing, and hiking, as well as indoor swimming with MITs Masters Swim Team. He also greatly enjoys an occasional sprint triathlon on summer weekends.

My favorite weekend in the Boston area, however, is a ferry ride down to Marthas Vineyard for a bike ride around the island, ending with a swim and lobster roll by the seaside in Edgartown, he says. I cant recommend it highly enough!

Read the rest here:
Deploying therapeutic payloads to cells - MIT News

CHICAGOWhen Merck & Co.s Keytruda won approval last week to treat tumors based on a common biomarkerrather than the location in the body where the tumor originated, talk was thatthe true start of precision medicine had arrived.

The $1.3 billion market cap biotech Loxo Oncology is hoping to be a part of that journey. At the American Society of Clinical Oncology meeting Saturday, Loxo posted the latest data for its experimental larotrectinib (LOXO-101), amedicationit hopes will treat an array of cancers innearly a dozen sites across the body.

The data showed that 50 larotrectinib patients withtumors harboring tropomyosin receptor kinase (TRK) fusions had a 76% objective response rate (ORR) across tumor types. The drug met its primary endpoint; key secondary endpoints, including progression-free survival and duration of response, had not yet been reached.

The data drewfrom three trials, a phase 1 study in adults, a phase 2 study called Navigate, and a phase 1/2 pediatric trial called Scout.The results were based on the intention-to-treat principle, using the first 55 TRK fusion patients enrolled to the three trials, regardless of their prior therapy or tumor-tissue diagnostic method.

In all, 44 adults and 12 younger patients were enrolled, with tumors identified by 14 different lab tests. The TRK fusion patients carried a host of primary diagnoses, including appendiceal cancer, breast cancer, cholangiocarcinoma, colorectal cancer, gastrointestinal stromal tumor, infantile fibrosarcoma, lung cancer and more.

The confirmed overall response rate was 76% in 50 patients, with these rates generally consistent across tumor types, TRK gene fusions, and various diagnostic tests, Loxo said in a statement.

In the pediatric setting, larotrectinib also showed promising activity in the presurgical management of patients with infantile fibrosarcoma, with three patients treated to best response.

The drug, developed in partnership with Array Biopharma,has a breakthrough designation from the FDA to treat children and adults with metastatic or inoperable solid tumors that test positive for the TRK biomarker, and who've either failed on previous treatments or have no acceptable alternatives.

In the safety department, Loxo says that seven(13%) of the study patients had their doses reduced because of side effects, but no patients stopped taking larotrectinib after suffering side effects.

All patients whose doses were lowered experienced tumor regression, which then continued on the reduced dose. Nearly all of the dose reductions were due to infrequent neurocognitive adverse events, likely a result of on-target TRK inhibition in the [central nervous system], Loxo explained.

Loxo added that sixpatients responded to larotrectinib but later progressed, a pattern referred to as acquired resistance.

The company is gathering other evidence forlarotrectinib'sapplication for FDA approval, slated for late this year or early next. Acentral, independent radiology review will be performed in the second half of 2017, and Loxo plans to announce that data before the end of the year. A separate assessment by independent radiologists, not yet conducted, will also be required to support its regulatory filing, the companynotes.

TRK is a neuron-stimulating factor that is active in fetal development but has its expression switched off later in life. In some cases, the TRK gene can fuse with other genes and reactivate, causing various forms of cancer.

Loxo's development program for the drug is agnostic to any particular tumor type, focusing instead on recruiting patients whose cancer cells express the TRK gene. If approved, the drug could be prescribed across multiple solid tumor types on the strength of genetic testing for neurotrophic TRK (NTRK) fusion proteins, which it will do with the help of Roche.

RELATED: Merck's Keytruda wins first FDA nod to treat genetically ID'd tumors anywhere in the body

NTRK mutations crop up in a small percentage of patients with any particular cancer, but they add up. The company estimated last year that between 1,500 and 5,000 late-stage cancer patients could be eligible for treatmentin the U.S. each year, with a similar number in Europe.

[T]he larotrectinib TRK fusion story fulfills the promise of precision medicine, where tumor genetics rather than tumor site of origin define the treatment approach," said David Hyman, lead investigator in the Navigate trial and chief of the early drug development service at Memorial Sloan Kettering Cancer Center."It is now incumbent upon the clinical oncology and pathology communities to examine our testing paradigms, so that TRK fusions and other actionable biomarkers become part of the standard patient workup."

The company also has two follow-up candidatesLOXO-292 and LOXO-195which target other cancer-causing genes resulting from fusions with kinase genes.

Original post:
Prepping for FDA filing, Loxo rolls up data on its site-agnostic cancer med larotrectinib - FierceBiotech

Carleton College will award the Bachelor of Arts degree to the 505 graduating members of the Class of 2017 onSaturday,June 10, in a ceremony beginning at 9:30 a.m. on the lawn west of Hulings Hall on the Carleton campus. A celebratory picnic on the Bald Spot will follow. In the event of severe weather, commencement will be held indoors at the Recreation Center. Seating is available to accommodate all guests, whether outdoors or indoors, and no tickets are required. The ceremony will also be broadcasted live online (https://apps.carleton.edu/events/commencement/livestream/).

Following President Steve Poskanzers opening remarks,Reina Desrouleaux '17, chemistry major from Silver Spring,Maryland (whose speech is titled [insert meaningful life experience here]) and Eli Ruffer '17, chemistry major from Highland Park, Illinois (whose speech is titled Tyler, the Prospective Student)will address the Class of 2017, families and friends, and faculty. In additionally, Carleton College will confer an honorary doctorate upon Kathy L. Hudson 82, former Deputy Director for Science, Outreach, and Policy at the National Institutes of Health, who will briefly address the class.

The highest honor given by the College, conferred honoris causafor the sake of honorthis years honorary degree recipient is Dr. Kathy L. Hudson, former Deputy Director for Science, Outreach, and Policy at the National Institutes of Health (NIH).

Throughout her distinguished career, Hudson has served the public by ensuring that advances in genomics and other rapidly moving areas of medical research are paired with wise and effective public policies.

After earning a B.A. in biology from Carleton College and a M.S. in microbiology from the University of Chicago, Hudson obtained her Ph.D. in molecular biology from the University of California, Berkeley. Although she trained for a career in research, Hudson discovered that her real passion was science policy. As an American Association for the Advancement of Science (AAAS) Fellow in Washington DC, she worked for the U.S. House of Representatives and then the Congressional Office of Technology Assessment.

After a stint in the office of the Assistant Secretary for Health at the Department of Health and Human Services, Hudson joined the National Human Genome Research Institute (NHGRI) as assistant director. While there she made a compelling case to scientists, public policy experts, and lawmakers about the need for federal legislation to guard against genetic discrimination. She also helped to broker an historic agreement between the public and private human genome projects, which was announced by President Bill Clinton in the White House in 2000.

In 2002, Hudson left NHGRI to found and direct the Genetics and Public Policy Center at Johns Hopkins University. She became a leader in educating and advising about science and policy issues in genetics. Also at Hopkins, Hudson was an Associate Professor in the Institute of Bioethics and the Institute of Genetic Medicine. It was Hudson who did much of the work to assemble the talented and dedicated team that, in 2008 after years of effort, achieved passage of the landmark Genetic Information Nondiscrimination Act.

In 2009, Hudson returned to the National Institutes of Health, becoming the Deputy Director for Science, Outreach, and Policy. In that capacity helped found and launch the National Center for Advancing Translational Sciences. She also had a major hand in the design and launch of three national scientific projects the BRAIN Initiative, the Precision Medicine Initiative, and the Cancer Moonshot. In addition, she led efforts to revise the rules that govern participation of human subjects in research, modernize clinical trial reporting, expand scientific data sharing, and develop appropriate oversight for rapidly moving areas of medical research, including stem cells and gene editing.

On top of her many duties and responsibilities, Hudson made time to serve as a strong and tireless advocate for the role of women in science. She personally mentored a group of young women who are now moving into key leadership roles with a wide range of innovative biomedical research and policy initiatives.

Earlier this year Hudson left government service, and is working as an advisor to companies and research institutes as they forge new directions at the forefront of biomedical research.

For further information, including disability accommodations, contact the Carleton College Office of College Communications at(507) 222-4309or emailkraadt@carleton.edu. The commencement site is located on the Carleton campus between College and Winona Streets in Northfield.

Read the original here:
Carleton College to hold its 143rd Commencement Ceremony June 10 - Carleton College News

Hillsboro native Dr. Nancy J. Cox was honored this spring as the first recipient of the Richard M. Caprioli Research Award. Dr. Cox is currently the director of the Vanderbilt Genetics Institute in Nashville, TN.

The daughter of the late Gene and Helen Cox, she is a 1974 graduate of Hillsboro High School and was selected as the second Hillsboro Education Foundation Distinguished Alumni Award recipient in 2002.

Dr. Cox earned her bachelor of science degree in biology from the University of Notre Dame in 1978 and her doctorate in human genetics from Yale University in 1982.

She completed a postdoctoral fellowship in genetic epidemiology at Washington University and was a research associate in human genetics at the University of Pennsylvania.

In 1987, she was hired at the University of Chicago. She was appointed full professor in the departments of medicine and human genetics in 2004 and chief of the section of genetic medicine the following year.

In 2012, she was named a University of Chicago Pritzker Scholar. In 2015, Dr. Cox was hired at Vanderbilt University School of Medicine as the Mary Phillips Edmonds Gray Professor of Genetics, founding director of the Vanderbilt Genetics Institute and director of the Division of Genetic Medicine in the Department of Medicine. She is a fellow of the American Association for the Advancement of Science

Throughout her career as a quantitative geneticist, Dr. Cox has sought to identify and characterize the genetic component to common human diseases and clinical phenotypes like pharmacogenomics traits (how genes affect drug response).

Her work has advanced methods for analyzing genetic and genomic data from a wide range of complex traits and diseases, including breast cancer, diabetes, autism, schizophrenia, bipolar disorder, Tourette syndrome, obsessive-compulsive disorder, stuttering and speech and language impairment.

Through the national Genotype Tissue Expression (GTEx) project, Dr. Cox also contributed to the development of genome predictors of the expression of genes, and she also has investigated the genetics of cardiometabolic phenotypes such as lipids, diabetes and cardiovascular disease.

With colleagues at the University of Michigan, Dr. Cox is generating content for the Accelerating Medicine Partnership between the National Institutes of Health (NIH), U.S. Food and Drug Administration, biopharmaceutical companies and non-profit organizations. The goal of the partnership is to identify and validate promising biological targets, increase the number of new diagnostics and therapies for patients, and reduce the cost and time it takes to develop them.

Dr. Cox is co-principal investigator of an analytic center within the Centers for Common Disease Genomics, another NIH initiative that is using genome sequencing to explore the genomic contributions to common diseases such as heart disease, diabetes, stroke and autism. A major resource for the Cox lab is Vanderbilts massive biobank, BioVU, which contains DNA samples from more than 230,000 individuals that are linked to de-identified electronic health records.

Dr. Cox is the author or co-author of more than 300 peer-reviewed scientific articles. She is former editor-in-chief of the journal Genetic Epidemiology, and is the current president of the American Society of Human Genetics.

For developing new methods that have aided researchers worldwide in identifying and characterizing of the genetic and genomic underpinnings of diseases and complex traits, Dr. Cox is the first recipient of the inaugural Richard M. Caprioli Research Award.

Dr. Cox and her husband, Dr. Paul Epstein live in Nashville, TN, and have two grown daughters, Bonnie Epstein and Carrie Epstein.

Read the original post:
Hillsboro Native Earns Honors At Vanderbilt - thejournal-news.net

June 1, 2017 This microscopic image of fibroblast cells shows the induction of cell fusion by a newly described gene and its protein, called myomerger. Multi-nucleus cells expressing genes needed to form skeletal muscle can be seen in flower-like clumps forming as cells fuse together. Reporting results in Nature Communications, the researchers seek ways to develop regenerative therapies for muscle disorders by getting stem cells to fuse and form functioning skeletal muscle tissues. Credit: Cincinnati Children's

A detour on the road to regenerative medicine for people with muscular disorders is figuring out how to coax muscle stem cells to fuse together and form functioning skeletal muscle tissues. A study published June 1 by Nature Communications reports scientists identify a new gene essential to this process, shedding new light on possible new therapeutic strategies.

Led by researchers at the Cincinnati Children's Hospital Medical Center Heart Institute, the study demonstrates the gene Gm7325 and its protein - which the scientists named "myomerger" - prompt muscle stem cells to fuse and develop skeletal muscles the body needs to move and survive. They also show that myomerger works with another gene, Tmem8c, and its associated protein "myomaker" to fuse cells that normally would not.

In laboratory tests on embryonic mice engineered to not express myomerger in skeletal muscle, the animals did not develop enough muscle fiber to live.

"These findings stimulate new avenues for cell therapy approaches for regenerative medicine," said Douglas Millay, PhD, study senior investigator and a scientist in the Division of Molecular Cardiovascular Biology at Cincinnati Children's. "This includes the potential for cells expressing myomaker and myomerger to be loaded with therapeutic material and then fused to diseased tissue. An example would be muscular dystrophy, which is a devastating genetic muscle disease. The fusion technology possibly could be harnessed to provide muscle cells with a normal copy of the missing gene."

Bio-Pioneering in Reverse

One of the molecular mysteries hindering development of regenerative therapy for muscles is uncovering the precise genetic and molecular processes that cause skeletal muscle stem cells (called myoblasts) to fuse and form the striated muscle fibers that allow movement. Millay and his colleagues are identifying, deconstructing and analyzing these processes to search for new therapeutic clues.

Genetic degenerative disorders of the muscle number in the dozens, but are rare in the overall population, according to the National Institutes of Health. The major categories of these devastating wasting diseases include: muscular dystrophy, congenital myopathy and metabolic myopathy. Muscular dystrophies are a group of more than 30 genetic diseases characterized by progressive weakness and degeneration of the skeletal muscles that control movement. The most common form is Duchenne MD.

Molecular Sleuthing

A previous study authored by Millay in 2014 identified myomaker and its gene through bioinformatic analysis. Myomaker is also required for myoblast stem cells to fuse. However, it was clear from that work that myomaker did not work alone and needed a partner to drive the fusion process. The current study indicates that myomerger is the missing link for fusion, and that both genes are absolutely required for fusion to occur, according to the researchers.

To find additional genes that regulate fusion, Millay's team screened for those activated by expression of a protein called MyoD, which is the primary initiator of the all the genes that make muscle. The team focused on the top 100 genes induced by MyoD (including GM7325/myomerger) and designed a screen to test the factors that could function within and across cell membranes. They also looked for genes not previously studied for having a role in fusing muscle stem cells. These analyses eventually pointed to a previously uncharacterized gene listed in the database - Gm7325.

Researchers then tested cell cultures and mouse models by using a gene editing process called CRISPR-Cas9 to demonstrate how the presence or absence of myomaker and myomerger - both individually and in unison - affect cell fusion and muscle formation. These tests indicate that myomerger-deficient muscle cells called myocytes differentiate and form the contractile unit of muscle (sarcomeres), but they do not join together to form fully functioning muscle tissue.

Looking Ahead

The researchers are building on their current findings, which they say establishes a system for reconstituting cell fusion in mammalian cells, a feat not yet achieved by biomedical science.

For example, beyond the cell fusion effects of myomaker and myomerger, it isn't known how myomaker or myomerger induce cell membrane fusion. Knowing these details would be crucial to developing potential therapeutic strategies in the future, according to Millay. This study identifies myomerger as a fundmentally required protein for muscle development using cell culture and laboratory mouse models.

The authors emphasize that extensive additional research will be required to determine if these results can be translated to a clinical setting.

Explore further: Researchers turn stem cells into somites, precursors to skeletal muscle, cartilage and bone

More information: Nature Communications (2017). DOI: 10.1038/NCOMMS15665

Adding just the right mixture of signaling moleculesproteins involved in developmentto human stem cells can coax them to resemble somites, which are groups of cells that give rise to skeletal muscles, bones, and cartilage ...

A team led by Jean-Franois Ct, researcher at the IRCM, identified a ''conductor'' in the development of muscle tissue. The discovery, published online yesterday by the scientific journal Proceedings of the National ...

Athletes, the elderly and those with degenerative muscle disease would all benefit from accelerated muscle repair. When skeletal muscles, those connected to the bone, are injured, muscle stem cells wake up from a dormant ...

Johns Hopkins researchers report they have inadvertently found a way to make human muscle cells bearing genetic mutations from people with Duchenne muscular dystrophy (DMD).

Duchenne muscular dystrophy is a chronic disease causing severe muscle degeneration that is ultimately fatal. As the disease progresses, muscle precursor cells lose the ability to create new musclar tissue, leading to faster ...

Researchers at Sanford Burnham Prebys Medical Research Institute (SBP) have conclusively identified the protein complex that controls the genes needed to repair skeletal muscle. The discovery clears up deep-rooted conflicting ...

A University of California, Berkeley, study of mice reveals, for the first time, how puberty hormones might impede some aspects of flexible youthful learning.

The bacteria in a child's gut appears to be influenced as early as its first year by ethnicity and breastfeeding, according to a new study from McMaster University.

The human body runs according to a roughly 24-hour cycle, controlled by a "master" clock in the brain and peripheral clocks in other parts of the body that are synchronized according to external cues, including light. Now, ...

A detour on the road to regenerative medicine for people with muscular disorders is figuring out how to coax muscle stem cells to fuse together and form functioning skeletal muscle tissues. A study published June 1 by Nature ...

Cholesterol, a naturally occurring compound at the lung surface, has been shown to have a clear effect on the properties of this nanoscale film that covers the inside of our lungs. Cholesterol levels in this system may affect ...

Researchers from Monash University have developed a new drug delivery strategy able to block pain within the nerve cells, in what could be a major development of an immediate and long lasting treatment for pain.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Link:
One gene closer to regenerative therapy for muscular disorders - Medical Xpress

What happened

Shares of gene editing pioneer Editas Medicine (NASDAQ:EDIT) dropped nearly 16% today after a new study published in Nature Methods drew attention to unintended effects of using the highly touted genetic engineering tool known as CRISPR. Shares of genome-editing peers CRISPR Therapeutics (NASDAQ:CRSP) and Intellia Therapeutics (NASDAQ:NTLA) were down as much as 6.9% and 14.9%, respectively, on the news.

The study, conducted by a team from Columbia University Medical Center, provided data showing that the technology can "introduce hundreds of unintended mutations into the genome," according to Genetic Engineering & Biotechnology News. That contradicts one of the better-known characteristics of CRISPR: precision.

Simply put, it's not sitting well with investors, who are (in knee-jerk fashion) adjusting the value placed on early-stage platforms, especially Editas Medicine, which will be the first of the group to enter clinical trials. As of 3:31 p.m. EDT, the stock had settled to a 11.3% loss.

Image source: Getty Images.

The study is among the first to quantify the specificity of CRISPR tools, which work by delivering gene editing enzymes to specific parts of the genome through the use of synthetic guide RNAs. Or that's how they're supposed to work. The authors of the study show that although intended edits can be made with respectable efficiency, such as correcting a mutation in a gene that causes blindness in mice, there are also unintended secondary edits made to the genome.

This may seem like a bombshell report, but it's a matter of optics. Researchers have never shied away from the reality that CRISPR gene editing tools can stray off target and make unintended edits to genomes in mammalian cells (i.e., humans). Many labs -- including Editas Medicine, CRISPR Therapeutics, and Intellia Therapeutics -- are working on increasing the efficiency and specificity of the technology. This is how science works. By quantifying these off-target mutations, which the paper attempted to do, researchers can begin to better understand how to improve the technology.

Investors and traders did not take the same cool-headed approach to the news, instead giving into a knee-jerk reaction to adjust the value of each pre-clinical technology platform. While off-target edits could prove troublesome for a CRISPR therapeutic used in humans, it's important to remember that there are currently no clinical trials underway in the United States. Editas Medicine will become the first to initiate a clinical trial later this year.

The sharp contrasts in reactions from researchers and investors is likely driven by how CRISPR is perceived by the media. Unfortunately, there is a generous amount of hyped-up science journalism that sticks to simple narratives -- "CRISPR has arrived and will cure all diseases!" -- instead of more nuanced takes that give equal weight to each current obstacles and future potential facing an emerging technology. Just remember: Biology is never quite so simple.

The results from the study don't really change anything, except for bringing more attention to the already existent clinical risk inherent to the development of early-stage CRISPR therapeutics. There is still plenty of work and new technology left to be developed before gene editing fulfills its promise in treating and curing human diseases. Hopefully, this can be a long-term positive for investors in CRISPR stocks by forcing them to listen to the fundamental hurdles for the technology. Hopefully.

Maxx Chatsko has no position in any stocks mentioned. The Motley Fool has no position in any of the stocks mentioned. The Motley Fool has a disclosure policy.

Read the rest here:
Here's Why Editas Medicine Fell as Much as 15.7% Today - Motley Fool

In Brief The CRISPR process will be used inside the human body for the first time on July 15th to combat HPV, which impacts millions of people worldwide. And this is just one of a huge amount of proposed CRISPR studies occurring soon. Uninvasive CRISPR

A new CRISPR trial, which hopes to eliminate thehuman papillomavirus (HPV), is set to be the first to attempt to use thetechnique inside the human body. In the non-invasive treatment, scientists will apply a gel that carries the necessary DNA coding for the CRISPR machinery to the cervixes of 60 women between the ages of 18 and 50. The team aims to disable the tumor growth mechanism in HPV cells.

The trial stands in contradistinction to the usual CRISPR method of extracting cells and re-injecting them into the affected area; although it will still use the Cas9 enzyme (which acts as a pair of molecular scissors) and guiding RNA that is typical of the process.

20 trials are set to begin in the rest of 2017 and early 2018. Most of the research will occur in China, and will focus on disabling cancers PD-1 gene that fools the human immune system into not attacking the cells. Different trials are focusing on different types of cancer including breast, bladder, esophageal, kidney, and prostate cancers.

The study, if it succeeds, will be promising for sufferers of HPV and act as a milestone in the CRISPR process. Although HPV is not necessarily cancerous, it cancause cervical cancer. In the U.S. alone, there are more than 3 million new infections every year.Although there is a vaccine for the virus, currently, once you have it you can never get rid of it.

More generally, the CRISPR process could be nothing short of a miracle: if it passes all medical tests it wouldnt just make medicine a whole new kettle of fish, it would reinvent the kettleand the fish, for almost any field. It is cheaper than other gene editing therapies, and could potentially save millions of lives by curing diseases we can only deal with therapeutically like cancer, diabetes and cystic-fibrosis. Crops could be altered more effectively using the process. Drugs and materials that were never possible before could be pioneered.

However, it is still extremely nascent technology, and many fear that there could also be a host of unexpected consequences. Recently, it has been found that it causes hundreds of unexpected mutations in DNA. While these concerns are valid, more research is necessary. Which is why the upcoming studies over the next few years are so vital to the future of our health.

Read the original here:
A World First CRISPR Trial Will Edit Genes Inside the Human Body - Futurism