Myonexus Therapeutics Starts Trial of First-Ever Gene Therapy for Rare Type of Muscular Dystrophy

November 8, 2018
  • In a mouse model, greater than 95% of muscle cells produced the beta-sarcoglycan protein after a single application
  • Myonexus and Sarepta are advancing four additional candidates
  • Sarepta has the option to purchase Myonexus at any point during their collaboration


Myonexus Therapeutics and Sarepta Therapeutics, announced on 11/8/18 the initiation of a clinical trial evaluating MYO-101, a novel gene therapy candidate for beta-sarcoglycanopathy, also known as LGMD2E. The goal is to deliver to skeletal and cardiac muscle a gene that codes for and enables robust and functional expression of the protein beta-sarcoglycan, the lack of which causes LGMD2E. The first patient in cohort 1 of the trial was dosed earlier in October and all patients in cohort 1 are expected to be dosed in 2018, with data expected by early 2019.

LGMD2E is a rare, degenerative and universally fatal form of muscular dystrophy caused by a genetic mutation. Progressive muscle fiber loss, inflammation and scarring in these patients causes degeneration of muscle strength and function. One of the leading causes of early mortality is cardiomyopathy caused by damage to the heart tissue.

“By implementing highly precise vector technology, gene therapy has great potential to deliver functionally curative solutions for challenging rare diseases. Based on positive pre-clinical results in both efficacy and safety, we are confident in the vector and platform selected for MYO-101 and are hopeful that MYO-101 could be the first profound therapy for patients with LGMD2E,” said Michael Triplett, Myonexus’ president and chief executive officer. “We look forward to working with the LGMD community and believe that by listening and incorporating their feedback, together we will make a dramatic impact on the progression of this disease.”

The Myonexus gene therapy platform, which uses the AAVrh.74 vector system, has been evaluated by a research team including Louise Rodino-Klapac, Ph.D. and Jerry R Mendell, M.D., and colleagues at Nationwide Children’s Hospital for more than 12 years before being licensed to Myonexus, an independent start-up company formed in 2017. Dr. Rodino-Klapac remains Myonexus’ chief scientific officer for the program while Dr. Mendell remains the principal investigator at Nationwide Children’s Hospital.

Pre-clinical studies of MYO-101 have demonstrated robust transduction of the vector to skeletal and cardiac muscle, with no therapy-limiting immune response. After a single administration of MYO-101 in a mouse model, greater than 95% of muscle cells produced the beta-sarcoglycan protein, and key parameters of function including strength and cardiac output were normalized. The treatment was associated with a positive increase in muscle fiber diameters, reduced scarring and fat infiltration, and improved overall activity compared with non-treated mice.

“Having evaluated the vector used in MYO-101 for more than a decade, in pre-clinical studies we have seen the robust and consistent ability of the vector to transduce the skeletal and cardiac muscle and produce a significant restoration of the missing protein,” said Dr. Louise Rodino-Klapac, who also serves as Vice President of Gene Therapy for Sarepta Therapeutics. “If successful in our clinical trial, this could become the first corrective treatment for LGMD2E, a merciless disease that has invariably robbed patients of strength and then life.”

Myonexus and Sarepta are advancing a series of therapies as part of their ongoing agreement. In addition to the clinical research underway on MYO-101, Myonexus is advancing four other candidates, all using the same AAVrh.74 vector: MYO-102 for LGMD2D, MYO-103 for LGMD2C, MYO-201 for LGMD2B, and MYO-301 for LGMD2L. Pursuant to the collaboration agreement, Sarepta will make milestone and other payments over a two-year evaluation period and has the option to acquire Myonexus at set terms at any time.

Under terms of the agreement, Sarepta made an upfront payment of $60 million and could make additional payments of $45 million over the next two years if all milestones are met.



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