In a study that demonstrates the promise of cell-based therapies for diseases that have proved intractable to modern medicine, 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), a fatal neuromuscular disorder also known as Lou Gehrig's disease.
The new work, conducted in a rat model and reported in the online, open-access journal from the Public Library of Science, PLoS ONE, shows that stem cells engineered to secrete a key growth factor can protect the motor neurons that waste away as a result of ALS. An important caveat, however, 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," explains Clive Svendsen, a neuroscientist who, with colleague Masatoshi Suzuki, led the study at UW-Madison's Waisman Center. "But when we looked at the function of these animals, we saw no improvement. The muscles aren't responding."
At present, there are no effective treatments for ALS, which afflicts roughly 40,000 people in the United States and which is almost always fatal within three to five years of diagnosis. Patients gradually experience progressive muscle weakness and paralysis as the motor neurons that control muscles are destroyed by the disease. The cause of ALS is unknown.
In the new Wisconsin study, nascent brain cells known as neural progenitor cells 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 that is very 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 has a very high affinity for motor neurons in the spinal cord," says Svendsen. When implanted, "the (GDNF secreting) cells survive beautifully. In 80 percent of the animals, we saw nice maturing transplants."
The implanted cells, in fact, demonstrated an affinity for the areas of the spinal cord where motor neurons were dying. According to Svendsen, the cells migrate to the area of damage where they "just sit and release GDNF."