Experimental gene therapy cassettes for Duchenne muscular dystrophy have been modified to deliver better performance. The cassettes, which carry the therapy into muscle cells, contain newer versions of a miniaturized treatment gene. The micro-dystrophin, as the treatment gene is called, has been restructured to enhance its functionality.
The revamped versions were developed and tested at UW Medicine labs in animal models of muscular dystrophy. The results will be published Feb. 1 in Molecular Therapy, a Cell Press journal.
Duchene muscular dystrophy is a life-shortening genetic disorder characterized by debilitating muscle weakness that gets worse with time. The condition almost exclusively affects males. It’s caused by X chromosome mutations that interfere with the production of dystrophins, which build and maintain healthy muscles.
Viral vectors are being explored as cargo ships for administering gene therapy for several kinds of diseases. For Duchene muscular dystrophy, researchers are designing and testing vectors that send therapy directly into muscle cells. Some of these vectors target the mutations. Others ferry in a synthetic dystrophin gene.
The treatment-carrying vehicles are re-tooled from small, adeno-associated viruses. These repurposed viruses can still enter human cells. Adeno-associated viruses do not cause infections, but can evoke an immune response that is usually mild.
Earlier versions of the UW Medicine-developed treatment cassettes did significantly enhanced muscle function in previous lab studies, but did not do so completely. That’s partly because the scientists have to condense the huge dystrophin gene to make it fit inside the transports virus.
Jeffrey S. Chamberlain, professor of neurology, medicine and biochemistry at the University of Washington School of Medicine, has been continuously involved in this research, from the invention of his lab’s original gene therapy cassettes to their recent revamping. His group was the first to show that adeno-associated viral vectors could deliver genes to muscles, body-wide.
