New hope for ALS seen with genetic techniques, growth factors

SAN DIEGO, Oct. 24 -- Cell transplants, silencing mutant genes, and use of a neuron support factor may represent new ways to treat the fatal brain disorder amyotrophic lateral sclerosis (ALS).

Research suggests that implanting cells to support the motor neurons that die off in ALS can help stave off the disease. Another group has developed technology to "silence" the mutant gene that causes ALS. And a third group of scientists found that a support factor rescues motor neurons and could be of value in treating ALS.

Also called Lou Gehrig's disease, ALS is a progressive neurological disease that paralyzes its victims by harming nerve cells that control muscles. The estimated 5,000 Americans newly diagnosed each year experience progressive muscle weakness that can hinder movement, speech, and even swallowing and breathing. Most cases of the disease are "sporadic"--that is, they occur out of the blue. About 5 percent of cases are inherited, and result from mutations in genes expressed in all tissues of the body, but that mysteriously affect only neurons that control muscles. The inherited form is clinically identical to the sporadic form.

Don Cleveland, PhD, and his colleagues at the University of California at San Diego created a mouse model of ALS with a mutation in the enzyme copper-zinc-superoxide dismutase (SOD1), which causes about 20 percent of the inherited forms of ALS, and about 1 to 2 percent of total cases.

They manipulated the mice's genes to give some cells mutant SOD1 and some normal SOD1. Curiously, the toxic effects of the SOD1 gene mutation have nothing to do with the enzyme's normal function. Instead, the mutation sends motor neurons down a cellular pathway to death by damaging not only the motor neurons but also their surrounding support cells. These support cells, called glia, provide important growth factors to neurons, and keep the surrounding environment clean and safe. When glia cells don't perform up to snuff

Contact: Leah Arinello
Society for Neuroscience

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