Experiments conducted in mice suggest gene therapy for type 2D Limb Girdle Muscular Dystrophy (LGMD2D) has the potential for safety and efficacy in humans with this serious muscle disease. The research team coordinated Dr. Jerry Mendell transferred human genes for the alpha-sarcoglycan protein, which is deficient in the muscles of people with LGMD2D, into mice lacking this muscle protein. In contrast to a previous study that suggested overproduction of alpha-sarcoglycan could have toxic effects in muscle tissue, this new study found intramuscular injections of the alpha-sarcoglycan gene to be safe and effective in the mice. In the present study, the researchers inserted alpha-sarcoglycan genes into transporters made from modified type 1 adeno-associated viruses (AAV1s) and attached different types of promoters. They injected these constructs into the tibialis anterior muscle of 4- to 5-week-old LGMD2D mice. With two of the promoters, muscle creatine kinase (MCK) and truncated MCK, the researchers saw sustained production of alpha-sarcoglycan protein in 60 percent to 70 percent of the fibers in the injected area six and then 12 weeks after the injections, without evidence of cytotoxicity. The other two promoters used were less effective with respect to high-level, sustained protein production. These findings support the use of gene therapy as a potential treatment approach for limb-girdle muscular dystrophy type 2D.

Neurology. 2008 Jul 22;71(4):240-7. Epub 2008 Jun 4.