01 Aug UW researchers show stem cell therapy may fight Lou Gehrig's disease
Madison, Wis. – Using engineered stem cells, a team of scientists from the University of Wisconsin-Madison has shown it is possible to rescue the dying neurons characteristic of amyotrophic lateral sclerosis (ALS), the fatal neuromuscular disorder also known as Lou Gehrig’s disease.
The new work, conducted in a rat model, was reported July 31 in the online, open-access journal from the Public Library of Science, PLoS ONE.
It demonstrates that stem cells engineered to secrete a key growth factor can protect the motor neurons that waste away as a result of ALS, the cause of which is unknown. An important caveat, according to UW-Madison neuroscientist Clive Svendsen, is that while the motor neurons within the spinal cord are protected by the growth factor, their ability to maintain connections with the muscles they control was not observed.
“At the early stages of disease, we saw almost 100 percent protection of motor neurons,” Svendsen said in a UW-Madison press release, “but when we looked at the function of these animals, we saw no improvement. The muscles aren’t responding.”
There are no effective treatments for ALS, which afflicts approximately 40,000 people in the United States and is almost always fatal within three to five years of diagnosis. ALS patients gradually experience progressive muscle weakness and paralysis as the motor neurons that control muscles are destroyed by the disease.
In the new Wisconsin study, nascent brain cells known as neural progenitor cells, which were derived from human fetal tissue, were engineered to secrete a chemical known as glial cell line derived neurotrophic factor (GDNF), an agent that has been shown to protect neurons but is difficult to deliver to specific regions of the brain. The engineered cells were then implanted in the spinal cords of rats afflicted with a form of ALS.
GDNF had a very high affinity for motor neurons in the spinal cord. When implanted, the GDNF-secreting cells “survive beautifully,” Svendsen said, “and in 80 percent of the animals, we saw nice maturing transplants.”
Perhaps more importantly, the implanted cells demonstrated an affinity for the areas of the spinal cord where motor neurons were dying. Svendsen said the cells migrate to the area of damage, where they “just sit and release GDNF.”
While the motor neurons exposed to GDNF were protected, the Wisconsin team was unable to detect the connections between the neurons and the muscles they govern.
The next step will be to determine the reasons that protected motor neurons are unable to hook up with muscles, but Svendsen said the work also supports movement toward clinical trials in humans.
“We think the cells are safe, and they do increase the survival of the motor neurons,” he said. “This may be very important for patients that lose neurons every day.”
Swendsen led the study at UW-Madison’s Waisman Center with colleague Masatoshi Suzuki. It was supported by grants from The ALS Association and the University of Wisconsin Foundation.
In addition to Svendsen and Suzuki, authors of the study include Jacalyn McHugh, Craig Tork, Brandon Shelly and Sandra M. Klein, all of the Waisman Center; and Patrick Aebischer, of the Swiss Ecole Polytechnique Fédérale de Lausanne.
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