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
- BENITEC BIOPHARMA INC. Management's Discussion and Analysis of Financial Condition and Results of Operations (form 10-Q) - Marketscreener.com - February 13th, 2023 [February 13th, 2023]
- CENTOGENE to Participate in Upcoming Conferences in February in the Lead Up to Rare Disease Day - Marketscreener.com - February 7th, 2023 [February 7th, 2023]
- Gene | Definition, Structure, Expression, & Facts | Britannica - January 27th, 2023 [January 27th, 2023]
- New gene therapy delivers treatment directly to brain - January 27th, 2023 [January 27th, 2023]
- Indian Pharma Congress: Gene-cell therapy, preventive medicine future of health care, says expert - Economic Times - January 25th, 2023 [January 25th, 2023]
- A blood test that identifies people at higher risk of miscarriage? Thats the goal of this award-winning Rutgers med student. - The Philadelphia... - January 19th, 2023 [January 19th, 2023]
- Gene Therapy: Genes As Medicine | Pfizer - January 6th, 2023 [January 6th, 2023]
- How Genomics will ensure a risk-free and beneficial treatment for good health and well-being - The Financial Express - December 28th, 2022 [December 28th, 2022]
- Regenerative Medicine Advanced Therapy Designation | FDA - December 18th, 2022 [December 18th, 2022]
- 3576 - Gene ResultCXCL8 C-X-C motif chemokine ligand 8 [ (human)] - November 23rd, 2022 [November 23rd, 2022]
- Study identifies new gene that drives colon cancer - EurekAlert - October 17th, 2022 [October 17th, 2022]
- Updated Stroke Gene Panels: Rapid evolution of knowledge on monogenic causes of stroke | European Journal of Human Genetics - Nature.com - October 17th, 2022 [October 17th, 2022]
- The challenges of translating CRISPR to the clinic - Labiotech.eu - October 17th, 2022 [October 17th, 2022]
- Editas Medicine Presents Preclinical Data on EDIT-103 for Rhodopsin-associated Autosomal Dominant Retinitis Pigmentosa at the European Society of Gene... - October 17th, 2022 [October 17th, 2022]
- 'We have to find a way': FDA seeks solutions to aid bespoke gene therapy - BioPharma Dive - October 17th, 2022 [October 17th, 2022]
- Mathematical model could bring us closer to effective stem cell therapies - Michigan Medicine - October 17th, 2022 [October 17th, 2022]
- Approval, Commercialization Highlighted at Cell & Gene Meeting on the Mesa - Genetic Engineering & Biotechnology News - October 17th, 2022 [October 17th, 2022]
- CANbridge-UMass Chan Medical School Gene Therapy Research in Oral Presentation at the European Society of Gene and Cell Therapy (ESGCT) 29th Annual... - October 17th, 2022 [October 17th, 2022]
- Depression Treatment: How Genetic Testing Can Help Find the Right Medication - Dunya News - October 17th, 2022 [October 17th, 2022]
- The Risk-Reward Proposition for CGT Clinical Trials - Applied Clinical Trials Online - October 17th, 2022 [October 17th, 2022]
- Precision Medicine Could Get Even More Precise With Allarity Therapeutics Next-Generation Diagnostics - Benzinga - October 17th, 2022 [October 17th, 2022]
- Decibel Therapeutics Receives FDA Clearance of IND Application for DB-OTO, a Gene Therapy Product Candidate Designed to Provide Hearing to Individuals... - October 17th, 2022 [October 17th, 2022]
- Time for your medicine: unlocking the power of our body clocks - The Guardian - October 17th, 2022 [October 17th, 2022]
- Replay establishes distinguished Scientific Advisory Board of genomic medicine and cell therapy experts - Yahoo Finance - October 17th, 2022 [October 17th, 2022]
- Scientists Reappraise the Role of Zombie Cells That Anti-aging Medicine Has Sought to Eliminate - Neuroscience News - October 17th, 2022 [October 17th, 2022]
- Forge Biologics Announces Updated Positive Clinical Data in RESKUE, a Novel Phase 1/2 Gene Therapy Trial for Patients with Krabbe Disease - Business... - October 17th, 2022 [October 17th, 2022]
- Gene Expression Signatures Are Analyzed for Biomarkers of Response in HCC - Targeted Oncology - October 17th, 2022 [October 17th, 2022]
- NHS England World-first national genetic testing service to deliver rapid life-saving checks for babies and kids - NHS England - October 17th, 2022 [October 17th, 2022]
- The proteinprotein relationship that could mend a broken heart - RegMedNet - October 17th, 2022 [October 17th, 2022]
- Study finds microprotein correlated to Alzheimers risk - Daily Trojan Online - October 11th, 2022 [October 11th, 2022]
- Passage Bio Announces Appointment of William Chou, M.D. as Chief Executive Officer - Yahoo Finance - October 11th, 2022 [October 11th, 2022]
- Gene Therapy Rapidly Improves Night Vision in Adults with Congenital Blindness - Newswise - October 11th, 2022 [October 11th, 2022]
- Scientists Discover Protein Partners that Could Heal Heart Muscle | Newsroom - UNC Health and UNC School of Medicine - October 11th, 2022 [October 11th, 2022]
- The Pros and Cons of Lentiviral and Adeno-Associated Viral Vectors - The Medicine Maker - October 11th, 2022 [October 11th, 2022]
- Insights & Outcomes: Foreign DNA, quantum potholes and relapsing fever - Yale News - October 11th, 2022 [October 11th, 2022]
- Expediting IND applications with drug master files - BioPharma Dive - October 11th, 2022 [October 11th, 2022]
- UNC School of Medicine Awarded $3 Million to Lead Study to Reduce PTSD Frequency, Severity | Newsroom - UNC Health and UNC School of Medicine - October 11th, 2022 [October 11th, 2022]
- Lineage to Present at Alliance for Regenerative Medicine 2022 Cell & Gene Meeting on the Mesa - businesswire.com - October 8th, 2022 [October 8th, 2022]
- The Next Crispr Gene Editing IPO Could Be Near - Henry Herald - October 8th, 2022 [October 8th, 2022]
- 10-year CRISPR anniversary: How gene editing revolutionized medicine, and what lies ahead - Genetic Literacy Project - October 8th, 2022 [October 8th, 2022]
- Blood from a baby at birth can be gene sequenced to prevent diseases - USA TODAY - October 8th, 2022 [October 8th, 2022]
- What doctors wish patients knew about breast-cancer prevention - American Medical Association - October 8th, 2022 [October 8th, 2022]
- Growth in Cell and Gene Therapy Market - Pharmaceutical Technology Magazine - October 8th, 2022 [October 8th, 2022]
- Gene Editing Service Market 2022 : Top Players to Reflect Impressive Growth Rate till 2029: Caribou Biosciences, CRISPR Therapeutics, Merck KGaA,... - October 8th, 2022 [October 8th, 2022]
- Tip Sheet: $78 million to support new precision oncology institute, update on experimental gene therapy for herpes and the launch of Fred Hutch's new... - October 8th, 2022 [October 8th, 2022]
- Cell and Gene Therapy: Rewriting the Future of Medicine - Technology Networks - October 2nd, 2022 [October 2nd, 2022]
- Growth in Cell and Gene Therapy Market - BioPharm International - October 2nd, 2022 [October 2nd, 2022]
- CRISPR Therapeutics Announces FDA Regenerative Medicine Advanced Therapy (RMAT) Designation Granted to CTX130 for the Treatment of Cutaneous T-Cell... - October 2nd, 2022 [October 2nd, 2022]
- BioMarin Resubmits Biologics License Application (BLA) for Valoctocogene Roxaparvovec AAV Gene Therapy for Severe Hemophilia A to the FDA - PR... - October 2nd, 2022 [October 2nd, 2022]
- Fighting Breast and Ovarian Cancer With a Lupus Antibody - Yale School of Medicine - October 2nd, 2022 [October 2nd, 2022]
- This gene therapy company is testing new tech to 'switch off' diabetes and obesity with a pill - Euronews - October 2nd, 2022 [October 2nd, 2022]
- Tenaya Therapeutics to Participate in Inaugural Hypertrophic Cardiomyopathy Medical Societys 2022 Scientific Sessions - Yahoo Finance - October 2nd, 2022 [October 2nd, 2022]
- Risk of Alzheimer's dementia may be predicted with help of new tool Washington University School of Medicine in St. Louis - Washington University... - October 2nd, 2022 [October 2nd, 2022]
- Tiny Sea Creature's Genes Shed Light on Evolution of Immunity - UPMC - October 2nd, 2022 [October 2nd, 2022]
- Who will get the call from Stockholm? It's time for STAT's 2022 Nobel Prize predictions - STAT - October 2nd, 2022 [October 2nd, 2022]
- Excision BioTherapeutics Awarded California Institute for Regenerative Medicine (CIRM) Grant to Support Ongoing Phase 1/2 Trial Evaluating EBT-101 as... - October 2nd, 2022 [October 2nd, 2022]
- NeuroVoices: Emma Ciafaloni, MD, on the Vast Expansion of Innovative Approaches to Duchenne Muscular Dystrophy - Neurology Live - October 2nd, 2022 [October 2nd, 2022]
- COVID mRNA Jabs and Testing Kicked Off This Industry of Drug Development: Here's What You Need to Know - The Epoch Times - October 2nd, 2022 [October 2nd, 2022]
- Kidney resident macrophages have distinct subpopulations and occupy distinct microenvironments - University of Alabama at Birmingham - October 2nd, 2022 [October 2nd, 2022]
- Nobel Prize for medicine: the full list of winners - The National - October 2nd, 2022 [October 2nd, 2022]
- The surprising link between circadian disruption and cancer may have to do with temperature - EurekAlert - October 2nd, 2022 [October 2nd, 2022]
- The global live cell imaging market is expected to grow at a CAGR of 8.44% during 2022-2027 - Yahoo Finance - October 2nd, 2022 [October 2nd, 2022]
- Chroma Medicine Announces Formation of Scientific Advisory Board of Global Experts in Gene Editing and Cell and Gene Therapy - PR Newswire - September 20th, 2022 [September 20th, 2022]
- Ring Therapeutics Announces Issuance of U.S. Patent for its Anellovector Compositions - Yahoo Finance - September 20th, 2022 [September 20th, 2022]
- Cholesterol gene mutation: Why would a healthy 27-year-old have severe heart problems? - 69News WFMZ-TV - September 20th, 2022 [September 20th, 2022]
- Gene Therapy for Severe Hemophilia B Could Be More Cost Effective Than Current Treatments - Managed Healthcare Executive - September 20th, 2022 [September 20th, 2022]
- AVROBIO Receives Rare Pediatric Disease Designation from U.S. Food and Drug Administration (FDA) for First Gene Therapy in Development for Cystinosis... - September 20th, 2022 [September 20th, 2022]
- The Biggest CGT Breakthroughs Through the Eyes of Our 2022 Power List - The Medicine Maker - September 20th, 2022 [September 20th, 2022]
- Leading Virus Researcher to Chair UVA's Department of Microbiology, Immunology and Cancer Biology - UVA Health Newsroom - September 20th, 2022 [September 20th, 2022]
- Work remains on Tay-Sachs and other Ashkenazi genetic disorders J. - The Jewish News of Northern California - September 20th, 2022 [September 20th, 2022]
- Study Shows Genetic Link to Moving to the Beat of Music - Newswise - September 20th, 2022 [September 20th, 2022]
- Viewpoint: In the post Roe v Wade world, what changes should a biology textbook writer make to address the medical repercussions of Dobbs? - Genetic... - September 20th, 2022 [September 20th, 2022]
- Alnylam Receives Approval in Europe for AMVUTTRA (vutrisiran) for the Treatment of Hereditary Transthyretin-mediated (hATTR) Amyloidosis in Adult... - September 20th, 2022 [September 20th, 2022]
- CSL flexes gene therapy muscle with latest drug - Sydney Morning Herald - September 20th, 2022 [September 20th, 2022]
- The MIT Press releases new book on the science of the heart from cardiac expert Dr. Sian Harding - EurekAlert - September 20th, 2022 [September 20th, 2022]
- Global Pharmaceutical Contract Manufacturing Market is projected to reach a market value of US$329.7 Billion in 2032: Visiongain Reports Ltd - Yahoo... - September 20th, 2022 [September 20th, 2022]
- Alzheon Reports Industry-Leading Biomarker, Brain Preservation and Clinical Effects Following 12 Months of Treatment in Phase 2 Trial of Oral ALZ-801... - September 20th, 2022 [September 20th, 2022]
- Do You Have Lung Cancer With An EGFR Mutation? If So, The Drug Tagrisso Might Be Right For You Based On New Results From A 'Practice Changing' Trial -... - September 20th, 2022 [September 20th, 2022]
- Getting rid of unwanted transformed cells: Possible new directions in cancer therapy - EurekAlert - September 20th, 2022 [September 20th, 2022]
- Sven Kili on reconvening with the ISCT - The Medicine Maker - September 14th, 2022 [September 14th, 2022]