Rachelle Crosbie-Watson, professor of neurology at the University of California, Los Angeles, was awarded an MDA research grant totaling $300,000 over a period of three years to study whether increasing levels of the sarcospan protein can be therapeutic for Duchenne muscular dystrophy (DMD) and other muscle diseases.
In DMD, one of the major consequences of loss of dystrophin protein is that the muscle membrane, called the sarcolemma, becomes less stable and easier to damage. Replacing lost dystrophin is one therapeutic strategy; increasing sarcolemma stability through other means is an alternative.
“We have discovered a novel method that improves sarcolemma stability and adhesion [holding together],” Crosbie-Watson says, and the current study is aimed at testing the mechanisms and feasibility of this novel approach in animal models of DMD, limb-girdle muscular dystrophy (LGMD) and congenital muscular dystrophy (CMD).
The method involves delivering the gene that codes for the sarcospan protein. Raising the level of sarcospan leads to multiple effects at the sarcolemma, all contributing to increasing its stability. “We have shown that sarcospan ameliorates muscular dystrophy in the dystrophin-deficient mouse model for DMD, and we rationalize that sarcospan treatment will also benefit other forms of muscular dystrophy resulting from loss of muscle cell adhesion,” she says. The advantage of this approach is that, unlike dystrophin, the sarcospan gene is small and easily accommodated in the safest gene therapy vectors. Crosbie-Watson will continue fine-tuning this approach in the DMD mouse model, and extend it to models of LGMD and CMD.
“The outcome of these experiments will contribute to a better understanding of the molecular events contributing to the ability of sarcospan to alter expression of proteins at the cell surface,” she says, “and reveal the efficacy of sarcospan for the treatment of other muscular dystrophies.”
Funding for this MDA grant began August 1, 2013.