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Swamping bad cells with good in ALS animal models helps sustain breathing
Date:10/19/2008

In a disease like ALS - one that's always fatal and that has a long history of research-resistant biology - finding a proof of principle in animal models is significant.

This week, Johns Hopkins researchers report that transplanting a new line of stem cell-like cells into rat models of the disease clearly shifts key signs of neurodegenerative disease in general and ALS in particular - slowing the animals' neuron loss and extending life.

The new work supports the hypothesis that artificially outnumbering unhealthy cells with healthy ones in targeted parts of the spinal cord preserves limb strength and breathing and can increase survival.

An account of the work appears online this week in Nature Neuroscience.

Two parts of the study hold special interest: One is that the target area for the added cells - parts of the cervical spinal cord that control the diaphragm muscles largely responsible for breathing - reap the most benefit. Forty-seven percent more motor neurons survived there than in untreated model animals. Respiratory failure from diaphragm weakness is the usual cause of death in ALS, also called Lou Gehrig's disease.

"While the added cells, in the long run, didn't save all of the nerves to the diaphragm, they did maintain its nerve's ability to function and stave off death significantly longer," says neuroscientist Nicholas Maragakis, M.D., an associate professor of neurology at Johns Hopkins who led the research team.

"We intentionally targeted the motor neurons in this region," he says, "since we knew that, as in ALS, their death results in respiratory decline."

Also significant is that the transplanted cells, called glial restricted precursors (GRPs), address a well-known flaw in people with ALS and in its animal models. Both humans and models are stunted in their ability to clear away the neurotransmitter glutamate. And excess glutamate - common in ALS - overstimulates the mo
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Contact: Maryalice Yakutchik
myakutc1@jhmi.edu
443-287-2251
Johns Hopkins Medical Institutions
Source:Eurekalert

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