UW News

October 4, 2001

Trials of new ALS treatment begin in mice

UW Health Sciences/UW Medicine

Researchers will test the effectiveness of “transforming growth factor alpha” infusions in mice who have a condition similar to the form of amytrophic lateral sclerosis (ALS) that runs in families.

ALS is commonly known in the United States as Lou Gehrig’s disease, after the late baseball star who had the disorder. It was also the disorder that took the life of Morris Schwartz, the Brandeis University professor whose final lessons were chronicled in the movie and the book, “Tuesdays with Morrie.”

ALS is marked by progressive loss of motor neurons in the brain and the spinal cord. The underlying cause, in some cases, is thought to be a mutation in the superoxide dismutase gene. This genetic defect leads to the buildup of toxic byproducts, such as free radicals. This genetic defect may account for 10 percent to 20 percent of ALS cases. Other mechanisms, such as neuron damage from neurotransmitters such as glutamate, are also implicated in this disorder.

Mice with a superoxide dismutase gene mutation have motor neuron loss resulting in diminished motor function and a shorter lifespan. Because their symptoms are similar to familial ALS, these mice have become a model for ALS research. The goal of such research is to slow disease progression and prolong survival.

Scientists became interested in the potential of transforming growth factor alpha in ALS research after University of California Irvine researchers studied its use in rats who had Parkinson-like symptoms. These studies suggested that infusing transforming growth factor alpha into the brains of these rats generated dopamine cells within the basal ganglia. These new cells arose from the proliferation, migration and differentiation of stem cells that originated within the subventrical zone of the rats’ brains.

Collaborative studies will soon be under way at the University of Washington, the University of California Irvine, and, Stem Cell Pharmaceuticals, Inc., a Seattle biotechnology company.

These studies are designed to see if transforming growth factor alpha might stimulate the familial ALS mouse’s own stem cells to replace dying motor neurons and also form glial cells, which make up the brain’s supportive structure. In addition, scientists are interested in seeing if transforming growth factor alpha protects motor neurons against oxidative damage, harm from neurotransmitters, and a shriveling form of cell death.

This strategy involves administering a drug that may perhaps encourage the recipient’s own stem cells to divide and ultimately replace lost neural cells. The researchers emphasized that this technique does not involve the transplantation of embryonic or adult donor stem cells.

The study is funded by a grant from Project ALS, a foundation created by members of the arts and entertainment industry to support ALS research. The co-principal investigators are Dr. Daniel Lazar and Dr. Michel Kliot, both from the UW Department of Neurosurgery; Nancy Schuman from the UW Department of Biobehavioral Nursing and Health Systems; and Dr. James Fallon from the Department of Neurobiology at the University of California Irvine.