LGMD2E or Beta-sarcoglycanopathy is an ultra-rare, severe, debilitating condition characterized by progressive muscle fiber loss, inflammation, and muscle fiber replacement with fat and fibrotic scars, leading to continually deteriorating muscle strength and function. Learn more about LGMD2E.
The goal of gene therapy for LGMD2E is to permanently enable the muscle cells to produce the critical beta-sarcoglycan protein via intravenous administration of a vector containing the beta-sarcoglycan gene and a promoter that only turns on the gene in muscle cells. Establishing beta-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 LGMD2E from genetic testing.
Research to date:
Studies of treatment with the gene therapy in the lab of L. Rodino-Klapac at Nationwide Children’s Hospital, in a beta-sarcoglycan production deficient mouse model, resulted in greater than 95% of muscle cells producing the protein, normalization of strength and resistance to fatigue in the diaphragm, decreased contraction-induced injury, and normalized cardiac output.
Treatment with the gene therapy was associated with increase in muscle fiber diameters, and a decrease in muscle scarring and fat infiltration. Treatment of beta-sarcoglycan deficient mice with the gene therapy was also associated with increase in overall activity versus non-treated mice. Treatment of normal, healthy, non-human primates with the gene therapy showed distribution and overexpression of the beta-sarcoglycan protein in muscles throughout the body without any adverse effects; no testing for functional changes were done since these were not beta-sarcoglycan deficient animals.
The first-in-human clinical trial of MYO-101 was initiated in late 2018 and is currently enrolling patients. Follow the link for more information.