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$7.2 million grant to aid search for ALS stem cell therapy

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Unread 09-20-2007, 05:14 PM   #1
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Thumbs Up $7.2 million grant to aid search for ALS stem cell therapy

$7.2 million grant to aid search for ALS stem cell therapy
Sept. 20, 2007

by Terry Devitt

With the help of a $7.2 million grant from the National Institutes of Health (NIH), a team of University of Wisconsin-Madison researchers will explore the potential of stem cells and natural growth factors to treat amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease.

The grant, to be awarded over five years, will fund research aimed at finding novel therapies for treating a debilitating and nearly always fatal condition caused by the withering of motor neurons, the brain cells that control the body's muscles.

"This is a great opportunity," says Clive Svendsen, who will direct the project along with UW-Madison neuroscientists Su-Chun Zhang and Gordon S. Mitchell. "There is a lot of synergy between our groups which provide for a lot of overlap that we think will help us get at some of the key issues of ALS."

The grant will support a combined cell-based approach to treating ALS, an incurable disease with no proven effective treatments. An estimated 30,000 people in the United States suffer from ALS, and most patients die within three to five years of diagnosis.

The new Wisconsin program will utilize both embryonic and fetal stem cells and will explore the possibility of stimulating healthy nerve cells to release growth factors and other chemicals to protect motor neurons.

The work will focus on three strategies for promoting healthy motor neurons and hitching new and rescued motor neurons to the muscles they control. The tri-fold approach will be tested in concert in a rat model for ALS.

Previous work at UW-Madison has shown that neural cells derived from fetal tissue and engineered to release a key growth factor known as GDNF, a chemical that promotes cell health, protected motor neurons in rats with ALS. However, the rescued nerve cells did not reattach to the muscles they control.

Studies to be supported by the new NIH grant will look at transplanting cells engineered to release the GDNF growth factor in combination with motor neurons derived from embryonic stem cells. The hope is there may be some synergistic effect between the two types of cells that not only protect and augment motor neurons in the animal model, but also promote connections with muscles. Zhang, a professor of anatomy in the UW-Madison School of Medicine and Public Health, has previously successfully derived motor neurons from embryonic stem cells.

"We're putting them right into the rat model and assessing their effects," explains Svendsen, a prominent stem cell researcher at UW-Madison's Waisman Center. "Motor neurons don't survive very well in transplants, and the hope is the cells in combination with GDNF release may promote a better result."

In addition, studies with intriguing potential to address the failure of the respiratory system in ALS, the ultimate cause of death for patients with the disease, are also planned. Despite the fundamental importance of respiratory failure in ALS, it has been little studied.

Work by Mitchell, a professor in the UW-Madison School of Veterinary Medicine, will explore the idea of using endogenous mechanisms in the body that seem to afford protection for motor neurons that control the respiratory system until the end stage of the disease. By inducing hypoxia, a condition where tissues are deprived of oxygen, the Wisconsin team hopes to prompt the release of growth factors that seem to have neuroprotective qualities on the respiratory motor neurons that drive the lungs.

The new grant, according to Svendsen, is important because it directly addresses key unexplored issues on the frontier of regenerative medicine, an emerging field that seeks to regenerate and replace diseased or damaged tissues and cells.



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