The neighborhood matters: Packard Center scientists show cell environment is import...( In amyotrophic lateral sclerosis (ALS)...),Health

ALS, or Lou Gehrig's disease, brings about a gradual death of the motor neurons that activate muscles. Paralysis follows. But according to work described today in the journal Science, the cells that are next to motor neurons -- but aren't themselves nerve cells -- can play a major role in advancing or limiting the disease.

"What we've been given is a new principle for extending survival or, perhaps, overcoming ALS, based on how many healthy cells surround an ailing motor nerve cell," says Don Cleveland, Ph.D., a scientist with The Packard Center for ALS Research at Johns Hopkins and, with Larry Goldstein, Ph.D., co-leader of the research team. "All this has great implications for stem cell therapy," he adds. "We now believe delivery of normal, non-neuronal cells to spinal cords could be completely protective, even without replacement of a single motor neuron."

In a series of experiments, the team measured the effect of having different proportions of healthy cells to at-risk cells in mice, clocking their survival time. Normally, the scientists work with standard animal models of ALS. Those mice or rats carry a mutant human gene -- called SOD1 -- that triggers a rare, inherited form of the disease in people. In these models, every cell carries a mutant SOD1 gene. The animals typically slip into death by the time they're six to eight months of age.

But in this study, the researchers used chimeric animals -- mice engineered to be a mix of normal cells, also called wild type, and cells containing the mutant SOD1 gene. They tagged the cells with molecular flags to make it clear which were which. The percent of wild-type cells in the animals' spinal cords ranged from 5 to 90 percent.

Having wild type cells mixed in had the effect of extending mouse survival from one to eight month
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
3-Oct-2003