LGMD2C is one of the most severe muscular dystrophies, affecting approximately 2 in a million newborns without regard to sex, race or national origin. The disease is an autosomal recessive genetic disorder, meaning the patient inherited one defective gamma-sarcoglycan gene each from both parents. The muscles most affected in LGMD2C are those surrounding the shoulder, hips and nearby muscles in the arms and legs. Symptoms of LGMD2C usually appear around 6-8 years of age and can progress to wheelchair dependence by 12-16 years of age. Enlargement of the calf muscle, tongue and heart are common, as are respiratory abnormalities. There is currently no cure or treatment for LGMD2C.
The goal of gene therapy for LGMD2C is to permanently enable the muscle cells to produce the critical gamma-sarcoglycan protein, after intravenous administration of a vector containing the gamma-sarcoglycan gene and a promoter that only turns on the gene in muscle cells. Establishment of gamma-sarcoglycan production in the muscle cells is expected to result in significant improvement in symptoms, with greater improvement toward normal the earlier in the disease the treatment is administered, and with the potential to prevent any symptoms of the disease from occurring when administered to newborns with confirmed LGMD2C from genetic testing.
The laboratory of L. Rodino-Klapac at Nationwide Children’s Hospital has and both safety and efficacy studies underway in a gamma-sarcoglycan deficient mouse model with early results looking promising. A pre-IND meeting with the FDA is planned for 2018 to present a plan for a systemic i.v. trial in LGMD2C patients.