March 15, 2007

Funding Renewed for Stem Cell Project Initiated by The ALS Association

[QUICK SUMMARY: Funding is continuing for a key stem cell project with expanded effort to focus on the glial cells that can be obtained to provide an array of trophic factors to support survival and healthy function of the motor neurons.]

Funding is continuing for a key stem cell project initiated by The ALS Association to produce a new therapeutic strategy for ALS. Clive Svendsen, Ph.D., and collaborators at the University of Wisconsin in Madison, are designing neural stem cells that one day might be developed for treating ALS patients, once the proof of principle is achieved in rats that reproduce key aspects of the disease.

In ALS, stem cells can rescue dying nerve cells by producing, at the site of damage, the supportive proteins called trophic factors. Svendsen and colleagues at the Waisman Center have achieved marked progress toward that goal by implanting into rat spinal cord stem cells engineered for increased production of glial derived neurotrophic factor (GDNF). Svendsen spoke to this progress in a talk he gave at a symposium on stem cells held at the conclusion of the annual meeting of the American Academy of Neurology in San Diego, California, April 2-8, 2006 and will soon publish the findings.

Tests with the cells engineered to produce GDNF show extended survival of the motor neurons near the site of their placement in the spinal cord, although life span was not extended in the rats with a mutation that produces the disease. Expanded effort will now focus on the glial cells that can be obtained through stem cells, as the glia make a vast array of trophic factors that can support the survival and healthy function of the motor neurons.

Svendsen is collaborating with an expert in respiratory physiology, Gordon Mitchell, Ph.D., to see if the stem cell therapy can slow or reverse the respiratory decline in the final stage of ALS. They have found that the changes in respiration with the disease may actually alter the disease course and may do so by changes in trophic factors.

To confirm this provocative finding, additional funding will be applied to determine the influence of oxygen supply on the survival of motor neurons in key brain and spinal cord areas.

The team will continue to work with rats that express a mutant form of the protein, copper-zinc superoxide dismutase (SOD1). This mutation is linked to some inherited forms of the disease. As ALS without a history of affected family members is clinically indistinguishable from inherited ALS, the rat outcome may have hope for all individuals affected by the disease.

The stem cells tested so far have been human, but it is possible that better results might be obtained in this particular instance with rat stem cells. Funding will be provided to examine the optimal cell type to use. Different drugs will also be tested to maximize the beneficial effect of glial cells on motor neuron survival, while avoiding the detrimental aspects of glial cell action in the disease process.

Stem cell therapy remains a promising option to explore for ALS therapy. Details of how such a strategy might be optimized should emerge from this collaboration.