Notes from 23rd annual meeting of the American Society for Gene and Cell Therapy

The American Society for Gene and Cell Therapy (ASGCT) annual meeting kicked off on Tuesday, May 12, 2020. Due to COVID-19, the meeting was held virtually. This meeting covers the field’s latest and most innovative science across all diseases and conditions. Several sessions were dedicated to muscular dystrophies, and four presentations focused on animal and cell studies related to LGMD2A/R1.

• Simone Spuler, Charité Medical Faculty and the Max-Delbrück-Center for Molecular Medicine, presented work developing a gene editing strategy to repair the CAPN3c.550delA mutation in LGMD2A/R1 patient-derived cells. This mutation is present in approximately 30% of LGMD2A/R1 patients, making it the most common LGMD2A-associated mutation. 
• Isabelle Richard, Genethon, sought to understand the effects of CAPN3 gene therapy on heart muscles. She found that administration of the gene therapy to healthy macaques was well-tolerated and caused no deleterious effects to the heart. Further, Dr. Richard suggests that mice are susceptible to cardiac toxicity due to a species-specific processing of the protein titin, and that this is less likely to occur in humans and primates. This work was funded in part by the C3 Gene Therapy initiative.
• Zarife Sahenk, Nationwide Children’s Hospital, had two presentations related to her preclinical studies developing a gene therapy for LGMD2A/R1. The first, a poster, examined biodistribution and toxicology, showing that mice that were administered systemic gene therapy express Calpain 3 protein in a variety of skeletal muscles. No toxicity was noted in any organs including the heart. In the second, an oral presentation, Dr. Sahenk showed that gene therapy treatment improved a mouse model of LGMD2A/R1 by increasing its ability to run on a treadmill and raising the amount of force its muscles could produce. Combined, these results suggest gene therapy has the potential to be a safe and effective treatment for LGMD2A/R1 patients. This work was funded in part by the C3 Gene Therapy Initiative.