2019 World Muscle Society Recap

The 24th International Annual Congress of the World Muscle Society was held October 1-5, 2019 in Copenhagen, Denmark. C3 Scientific Director Dr. Jennifer Levy represented Coalition to Cure Calpain 3 (C3) and presented a poster detailing the C3 mission, patient registry, and grant programs. The Congress covered a variety of topics related to advances across the neuromuscular field, including development of treatments of neuromuscular disorders. Among the highlights:

Jerry Mendell, Nationwide Children’s Hospital, presented an update on the Sarepta-sponsored clinical trial that utilizes AAV-medicated gene therapy to systemically deliver the SGCB gene to limb girdle muscular dystrophy type LGMD2E/R4 patients. At 9-months post treatment, patients show improved muscle function in all tests used. Additionally, their serum creatine kinase levels – a marker of muscle damage – decreased from pre-treatment levels. These results suggest that gene therapy is an effective approach to treating LGMDs. Click HERE to view the results and videos presented by Dr. Mendell.

Tina Dysgaard Jeppesen, Copenhagen Neuromusuclar Center, used stationary bike training to expose ambulatory LGMD2I/R9, LGMD2L/R12, and Becker Muscular Dystrophy patients to aerobic exercise. She found that this type of training is safe and increases endurance and strength. She predicts that aerobic exercise will benefit individuals with other types of muscular dystrophy as well. Patients should speak with their doctors before initiating a new exercise program.

Megan Iammarino, Nationwide Children’s Hospital, used several functional tests to show the disease trajectories of LGMD2A/R1, LGMD2B/R2, LGMD2D/R3, and LGMD2E/R4. The study included 184 total LGMD patients, 66 of whom had LGMD2A/R1. Several of these patients were assessed at the National LGMD Conference held in Chicago in August 2019. The authors found that different LGMD subtypes progress differently as patients age, indicating that caution should be taken when combining data from different subtypes in clinical research studies.

Jaakko Sarparanta, Folkhälsan Research Center and University of Helsinki, showed that titin, a protein that when mutated causes tibial muscular dystrophy and LGMD2J/R10, is normally processed into fragments. Calpain 3, the protein that is defective or missing in LGMD2A/R1, appears to play a role in titin processing. He is currently investigating the consequences of reduced Calpain 3 activity on titin processing. This work was funded in part by a grant from C3.

Jordi Díaz Manera, Hospital de la Santa Creu I Sant Pau de Barcelona, demonstrated that muscle MRI can be a useful measure of muscle changes in clinical trials. He showed that changes in MRI correlate with changes in muscle function and that this measure can be sensitive, reliable, and quantitative. MRI has the potential to be useful as an outcome measure for a variety of types of muscular dystrophy.

Natalie Miller, Nationwide Children’s Hospital, presented preliminary data using Fitbits to monitor activity in individuals with Duchenne Muscular Dystrophy and Limb Girdle Muscular Dystrophy. She found that activity monitoring via Fitbit could be a useful outcome measure in clinical trials, but one must consider the considerable seasonal variability due to a significant decrease in activity levels in the winter.

Stefanie Müthel, Charité Medical Faculty and the Max-Delbrück-Center for Molecular Medicine, shared her 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. Dr. Müthel previously received a C3 Travel Grant to present on this project at the Biology of Calpains in Health and Disease Conference in Pacific Grove, California.

2019 World Muscle Society Recap