(Philadelphia, PA) - Previous gene therapy approaches to treat muscular dystrophy have been hampered by an inability to successfully place the therapeutic genetic material into deficient muscle cells. Now, for the first time, using a naturally-occurring hamster model of limb girdle muscular dystrophy (LGMD), researchers at the University of Pennsylvania Health System have developed a technique that successfully produces widespread transfer of corrective genetic material into muscle cells throughout an entire limb. In so doing, the research team also found evidence for a cascade of events that eventually results in cellular destabilization - a process which manifests as muscle weakness in patients with this and other forms of muscular dystrophy.
It is hoped that the Penn-developed technique would be ultimately transferable to human clinical trials involving gene therapy treatments of many forms of muscular dystrophy, as well as other types of debilitating or fatal disorders - such as metabolic myopathy and cardiomyopathy (heart failure). "We've demonstrated proof of concept that the methodology can work for both skeletal and cardiac muscle," says principal author Hansell Stedman, MD, assistant professor of surgery at Penn's Institute for Human Gene Therapy, "so the next step will be to establish its safety and effectiveness in patients with this form of muscular dystrophy." Stedman cautions that clinical trials will have to address safety issues one step at a time before significant therapeutic benefit can be approached.
The research is being published as the cover article in the April 1999 issue of Nature Medicine.
Induced Vessel Leakage Nets Massive Cell Saturation
In limb girdle muscular dystrophy, the instability of muscle tissue is linked directly to the level of genetic disruption that occurs within the sarcoglycan complex - a critical muscle structure composed of four membrane-spanning proteins. Depending on the nature of
Contact: Rebecca Harmon
University of Pennsylvania School of Medicine