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Gene therapy delays death in mouse with symptoms of Lou Gehrig's disease

It's not a cure, but a novel form of gene therapy has delayed symptoms and almost doubled life expectancy in mice with the equivalent of Lou Gehrig's disease, a team from the Salk Institute and Johns Hopkins reports in the Aug. 8 issue of Science.

In experiments with mice destined to develop the condition, injection of the gene for insulin-like growth factor-1 (IGF-1) into muscles protected nerve cells, extended survival and improved strength, say the scientists, who are planning a clinical trial they hope to be able to begin in the next year.

The most beneficial treatment ever seen in the mice, it is also the first to extend animals' survival when given after symptoms develop, the researchers say. In the experimental mice and in people with the disease, known as amyotrophic lateral sclerosis or ALS, nerves that control muscles gradually die, leading to paralysis and death.

"ALS is a terrible disease and patients have few treatment options today. We're very excited about this," says Jeffrey Rothstein, M.D., Ph.D., professor of neurology and neuroscience and director of the Packard Center for ALS Research at Johns Hopkins. "Even in mice, progression of the disease is so rapid that we only test possible treatments before the mice get sick. It is amazing that this gene therapy can slow progression even after symptoms develop."

Gene therapies use a virus to deliver specific genetic instructions to cells and usually have to be delivered directly to where the gene is needed. But instead of injecting this "adeno-associated" virus into specific nerves in the brain and spinal cord -- a feat that is likely impossible -- researchers at the Salk discovered and took advantage of the virus's ability to migrate from muscle into the nerves that control them. The nerve cells then made the IGF-1 protein.

"IGF-1 protein has been used in clinical trials, but with marginal results," said Fred H. Gage, Ph.D., professor of genetics at the S
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
7-Aug-2003


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