Gene Therapy volunteers were evaluated at set intervals through 180 days, and therapy effectiveness was measured by assessing alpha-SG protein expression in the muscle, which was four to five times higher than in the muscles that received only the saline [placebo]. The volunteers encountered no adverse health events, and the transferred genes continued to produce the needed protein for at least six months after treatment.
Limb-girdle muscular dystrophy actually describes more than 19 disorders that occur because patients have a faulty alpha-sarcoglycan gene. In each of the disorders, the muscle fails to produce a protein essential for muscle fibers to thrive. It can occur in children or adults, and it causes their muscles to get weaker throughout their lifetimes. The trial evaluated the safety of a modified adeno-associated virus — an apparently harmless virus known as AAV that already exists in most people — as a vector to deliver the alpha-SG gene to muscle tissue.
It is easier to treat localized conditions. So the initial successes with gene therapy are for localized conditions. There have been several trials that have proved the safety of the new gene theraphy methods.
Muscle-fiber size increased in the treated areas, suggesting that it may be possible to combat the so-called “dystrophic process” that causes muscles to waste away during the course of the disease. Beyond muscular dystrophy, the discovery shows muscle tissue can be an effective avenue to deliver therapeutic genes for a variety of muscle disorders, including some that are resistant to treatment, such as inclusion body myositis, and in conditions where muscle is atrophied, such as in cancer and aging.
“These exciting results demonstrate the feasibility of gene therapy to treat limb-girdle muscular dystrophy,” said Jane Larkindale, portfolio director with Muscular Dystrophy Association Venture Philanthropy, a program that moves basic research into treatment development. “The lack of adverse events seen in this trial not only supports gene therapy for this disease, but it also supports such therapies for many other diseases.”