While dystrophin and alpha-sarcoglycan gene replacement focus on replacing mutated genes, Muscle Group studies have also shown value in some existing “healthy” genes. “Recent studies have highlighted the importance of genes that are not mutated in various forms of muscular dystrophy,” said Paul T. Martin, PhD, principal investigator in the Center for Gene Therapy and Muscle Group member. “These genes may serve as surrogates to protect skeletal muscle fibers from injury, despite the fact that they do not replace the genetic defect.”
One such gene is Galgt2. When this gene is overexpressed in skeletal muscle, it produces an excess of proteins known to bind to dystroglycan, a protein family implicated in numerous forms of muscular dystrophy. “In a sense, Galgt2 proteins serve as substitutes for the proteins that are missing in several types of muscular dystrophy,” said Dr. Martin.
Upon examining Galgt2 overexpression in mice models of three distinct forms of muscular dystrophy (Duchenne muscular dystrophy, limb girdle muscular dystrophy 2D, and one of the most severe forms laminin-deficient congenital muscular dystrophy), scientists found that the mice had significantly reduced symptoms of muscular dystrophy than those without excess Galgt2.
“This makes Galgt2 the first surrogate gene approach shown to prevent muscle pathology in these three forms of the disease,” said Dr. Martin. “These findings suggest that Galgt2 may have a broad spectrum of therapeutic potential for the treatment of various myopathies.”