Nerve-Nourishing Gene Shows Promise in Mice With Lou Gehrig's Disease
TUCSON, Ariz., April 18, 2002 — A researcher supported by the Muscular Dystrophy Association has used gene therapy to slow the progression of amyotrophic lateral sclerosis in mice, raising hopes for a similar treatment approach for people affected by the deadly, degenerative disorder.
Gyula Acsadi, an assistant professor in the Departments of Pediatrics and Neurology at Wayne State University in Detroit, was part of a team that inserted into mice with ALS genes that appear to preserve nerve cells. The gene slowed the disease course in the mice.
Acsadi presented the findings today at the 54th annual meeting of the American Academy of Neurology in Denver.
"Slowing disease progression by a similar degree in humans could add several years to the life of an ALS patient," Acsadi said.
ALS, also known as Lou Gehrig's disease, attacks adults of both sexes, usually in middle age. The disease destroys muscle-controlling nerve cells in the brain and spinal cord, leading to progressive paralysis and usually to death three to five years after onset.
In one set of experiments, which will be fully reported in the June 10 issue of Human Gene Therapy, mice were injected with genes for glial-derived neurotrophic factor (GDNF), a natural substance found in the body that's been shown to promote survival of nerve cells.
The scientists tucked each GDNF gene into an adenovirus and injected the gene-carrying viruses into the muscles of mice bred to have ALS. Acsadi said the GDNF genes or the protein the gene makes probably traveled from the injected muscles up into nerve cells via a process called retrograde transport.
The treated mice didn't show disease symptoms until an average of a week later than the untreated mice, and they survived an average of 17 days longer. Their movement-related function, tested by their ability to stay on a rotating rod, didn't start to decline until one to two weeks later than that of the untreated mice.
In a later set of experiments, the smaller and probably safer adeno-associated virus was used to insert the GDNF gene into mouse muscles, with similar results.
"Gene therapy for ALS has always been complicated by the need to penetrate formidable barriers around the brain and spinal cord," MDA Director of Research Development Sharon Hesterlee said. "This approach is innovative because it uses naturally occurring pathways in the body to transport therapeutic genes into the central nervous system."
MDA is a voluntary health agency working to defeat more than 40 neuromuscular diseases.
