Subject: Robert Packard Center ALS News Network


View this article online at: http://www.alscenter.org/news/briefs/080207.cfm

ALS MOUSE STUDY HIGHLIGHTS ASTROCYTES' STRONG POTENTIAL AS THERAPY TARGET

A new study that examines the role of astrocytes - cells intimately linked to the motor neurons affected by ALS - greatly shores up both their role in the disease and the idea that they'd be useful targets for therapy to slow its progress.

Effectively mimicking such therapy in focusing on the astrocytes in mouse models of ALS neither prevented the disease from starting nor from going into its early stages. But late disease progression was sharply delayed. Overall, the mice survived an average of 60 days longer. "That nearly doubles the life expectancy of ALS mice," says Don Cleveland, a Packard Center neuroscientist with the University of California, San Diego, "and therapeutically, that's the big news."

The work Cleveland reported this week in the online version of the journal Nature Neuroscience is part of a body of research he and colleagues are conducting to shed light on the biology of ALS by showing what part various nervous system cells and affected muscles play in the disease.

As yet, no one cause has been singled out for the most common, or sporadic, form of the disease. And though researchers have found genes for a variety of inherited types of it, including the mutated SOD1 gene in the most common familial ALS, exactly how they cause or advance the disease isn't clear. Cleveland's work was carried out in mice carrying the mutated SOD1 gene, the classic model of the illness.

"We know that the mutant gene's effects on motor neurons in some way trigger the onset of ALS," says Cleveland. "But accumulating evidence in our labs is showing that cells other than motor neurons play an active role in their ultimate decline and death."

Earlier work by a Cleveland team, for example, showed that microglia, small immune cells that inhabit the nervous system, also significantly speed motor neurons' downhill path.

In the new study, Cleveland used a complex genetic tactic to silence the mutant SOD1 gene, but only in astrocytes. Because those cells normally nourish motor neurons and scavenge toxins from their environment, keeping them healthy was likely responsible for the life-extending effect, he says.

"Our findings show that astrocytes are likely to be viable targets to slow the rate of disease spread and extend the life of patients with ALS," he adds. That may prove especially important to Packard and other scientists readying stem cells for human use. "This gives us a good idea what cells should be replaced using stem cell therapy," Cleveland says. "Astrocytes are very likely much easier to replace than the slow-growing motor neuron."

The work was supported by Packard Center grants as well as those from the NIH, the Muscular Dystrophy Association and others.


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About The Robert Packard Center for ALS Research at Johns Hopkins
www.alscenter.org

Located in Baltimore, the Robert Packard Center for ALS Research at Johns Hopkins is a collaboration of scientists worldwide, working aggressively to develop new treatments and a cure for amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. The Center is the only institution of its kind dedicated solely to the disease. Its research is meant to translate from the laboratory bench to the clinic in record time.

Scientists and clinician members of the Packard Center are unsurpassed at moving drugs reliably and rapidly from preclinical experiments to human trials. They're linked, directly or indirectly, to the world's major pharmaceutical and biotechnology companies, which have both infrastructure and experience to make promising drugs into therapies.

Packard Center scientists are the first to propose and test a combination approach to drug therapy, a tactic that has worked for AIDS, cancer and other diseases.

ALS is a devastating, progressive neuromuscular disease that causes complete paralysis and loss of function - including the ability to eat, speak and breathe. ALS progresses quickly and is not curable. Most patients die within five years of diagnosis.

For more information about The Robert Packard Center for ALS Research at Johns Hopkins, including information on its latest research and treatment, visit www.alscenter.org