P&S Journal: Winter 1998, Vol.18, No.1
Gene Therapy for ALS?
In mice genetically engineered to develop familial amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, over expression of the human proto-oncogene Bcl-2 may delay the onset of ALS, according to a study reported in a July 1997 issue of Science.
P&S researchers Drs. Vladimir Kostic, Vernice Jackson-Lewis, Serge Przedborski, and their colleagues at the Hopitaux Universitaires de Geneve made the discovery by working with two strains of transgenic mice: one carrying mutations that produce familial ALS and another carrying Bcl-2, which is known to protect against apoptosis. The Bcl-2 mice carried 16 copies of the gene to maximize any protective effect against ALS.
The researchers crossbred the two strains of mice and found that offspring inheriting both ALS and Bcl-2 developed ALS significantly later in life--and in fact lived longer--than offspring that inherited ALS but not Bcl-2.
The gene responsible for familial ALS is a mutant copper/zinc superoxide dismutase. The normal copper/zinc superoxide dismutase helps eliminate free radicals. People with a mutation of this gene presumably develop ALS because of free radical damage to their motor neurons. The study found that ALS mice carrying the Bcl-2 gene had both more and healthier motor neurons than ALS mice without Bcl-2.
The study suggests that gene therapy--either with Bcl-2 or with another gene capable of preventing apoptosis--could help delay the onset of ALS," says Dr. Przedborski, principal investigator and assistant professor of neurology. The finding also could lead to development of drugs that mimic proteins produced by Bcl-2 or other protective genes.