A follistatin gene therapy compound gains orphan drug status; potential improvements are reported for utrophin-based therapies, exon skipping and stem cell transplantation
Update (Jan. 23, 2013): The "Building better utrophin" section was updated to reflect the availability of a Jan. 22, 2013, press release from the University of Missouri.
Below is a wrap-up of recent research news about the development of therapies for Duchenne, Becker and limb-girdle muscular dystrophies.
Dongsheng Duan's interest in gene therapy to treat diseases goes back a long way, although his initial focus wasn't muscular dystrophy.
"I came to the muscle field by accident," says Duan, an MDA research grantee and professor of molecular microbiology and immunology at the University of Missouri at Columbia. "It was not something I intended to do when I was young."
Researcher Dongsheng Duan says adding a piece to miniaturized dystrophin genes makes them more effective
Displacement of a protein called neuronal nitric oxide synthase (nNOS) from the membrane that surrounds each skeletal muscle fiber appears to be a much more important contributor to exercise intolerance and even cardiac degeneration in some forms of muscular dystrophy than previously recognized.
Promising minigene only partially normalizes heart muscle
A promising “minidystrophin gene” that restores normal muscle force to skeletal and diaphragm muscles in mice with a disease resembling Duchenne muscular dystrophy (DMD) seems to be only partially effective at restoring strength and function to heart muscles.
Can sarcoglycan proteins help compensate for dystrophin's absence?
Delivering the gene for the missing dystrophin protein to the muscles of children and young men with Duchenne muscular dystrophy (DMD) is one of several therapeutic avenues under intense investigation in this disease. However, the strategy has technical drawbacks, and some experts worry that introduction of a previously absent protein could provoke a dangerous immune response.
Real progress is being made in supplying functional dystrophin genes to treat Duchenne muscular dystrophy (DMD), a disease in which mutated dystrophin genes keep this critical protein from being produced in muscle fibers.
An MDA-supported research team, testing gene transfer in dogs using adeno-associated viral (AAV) shells (vectors), noted an unwanted immune response, a factor they recommend be considered in human trials. The response occurred even when the vectors weren’t carrying any genes.
Until now, AAV transporters have been thought not to provoke much of an immune response.