Day Two Report from the 2018 New Direction in Biology and Disease of Skeletal Muscle Conference

The second day of the conference focused on gene editing, gene therapy as well as the latest research into the development of disease biomarkers.

Presentations included:

• Dongsheng Duan (University of Missouri) described his research groups efforts that led to the selection of an optimized micro dystrophin gene construct for systemic AAV deliver to Duchenne patients. This optimized sequence is currently being used by Solid Biosciences.
• Leonela Amoasii (University of Texas Southwestern Medical Center) presented the results from their latest study in the dystrophic dog model. Systemic deliver of CRISPR/Cas9-mediated genome editing restored very high levels of dystrophin expression.
• This result was mentioned (and expanded upon) in Mondays Keynote Address by Eric Olson (University of Texas Southwestern Medical Center). He talked about the use of CRISPR/Cas9-mediated genome editing to correct disease causing mutations in Duchenne. Exonics Therapeutics is developing this single-cut CRISPR gene editing therapy to treat Duchenne muscular dystrophy.
• Marco Passini (Sarepta Therapeutics) presented their latest research on systemic delivery of PPMO based oligonucleotides for enhanced exon skipping to treat Duchenne. The results are very encouraging. They demonstrated that the cell penetrating PPMO’s generated long lasting (up to 3 months) and robust effects. Dystrophin levels were sustained at high levels in all muscle groups in preclinical models. The first cell-penetrating PPMO is now in a Phase 1 clinical trial to evaluate the safety, tolerability, and pharmacokinetics of a single dose of SRP-5051 in Duchenne patients amenable to exon 51 skipping – link to clinical trial detailshttps://clinicaltrials.gov/ct2/show/NCT03375255?term=srp-5051&rank=1