Limb-Girdle MD Gene Saves Hamster Hearts

MDA grantees Xiao Xiao and Chunping Qiao at the University of Pittsburgh were part of a research team that recently announced it had successfully transferred genes for delta-sarcoglycan to hamsters missing this skeletal and cardiac muscle protein. This significantly improving their cardiac and whole-body functioning and extending their lives.

A lack of any of four sarcoglycan proteins, normally found in the membranes of muscle cells, leads to sarcoglycan-deficient limb-girdle muscular dystrophy (LGMD) in humans.

In a study published in the Oct. 25, 2005, issue of Circulation, Xiao and colleagues report that they gave delta-sarcoglycan genes, encased in type 8 adeno-associated virus (AAV) shells, to LGMD-affected hamsters by injecting the genes only once into the abdomen or into a vein.

Even months later, heart function and appearance, along with the ability to run on a treadmill, were markedly better than in an untreated group, and all the treated hamsters were alive at the end of the nearly year-long study.

The researchers found that the AAV8 shell was extremely effective in delivering the therapeutic genes to heart, diaphragm and skeletal muscles but that it also delivered them to other tissues. They overcame this problem by attaching a muscle-specific "on switch" (promoter) to the gene, so that delta-sarcoglycan wouldn't accumulate in unwanted tissues, such as the liver. Even adult animals, with mature immune systems, didn't reject the therapeutic gene or protein.

The study's authors write, "The unprecedented gene delivery efficiency and therapeutic efficacy for both cardiomyopathy and muscular dystrophy demonstrated here in an animal model should pave the way for further preclinical studies... and eventually in clinical trials for this and other genetic diseases."