2012 Grants - Blurton-Jones

Testing the Therapeutic Efficacy of Neprilysin-Expressing Neural Stem Cells

Mathew M. Blurton-Jones, Ph.D.
University of California, Irvine
Irvine, California

2012 New Investigator Research Grant

Neural stem cells have the potential to develop into any type of brain cell. In diseased brains, these cells tend to migrate to areas that have become injured or inflamed. Recent studies have found that when neural stem cells are transplanted into the brains of Alzheimer's-like mice, they can improve the animals' cognitive function. However, the treatment has so far had no effect on underlying Alzheimer's pathologies—such as the brain accumulations of abnormal tau protein and the protein fragment beta-amyloid. If stem cell therapy cannot rid the brain of harmful beta-amyloid and tau, then it will likely lose its ability to ameliorate cognitive decline as Alzheimer's progresses.

Mathew M. Blurton-Jones, Ph.D., and colleagues have been studying how to make neural stem cells more effective at battling Alzheimer's-related brain changes. They have developed stem cells that express neprilysin, an enzyme (biological molecules that increase the rates of chemical reactions) that can help degrade beta-amyloid in the brain. These cells can be made to act as "vehicles" for transporting neprilysin to areas of amyloid clumping. In preliminary experiments, the researchers have found that their modified neural stem cells can degrade beta-amyloid plaques (clumps) in living mice. But the long-term cognitive effects of this treatment remain unknown.

For the current study, Dr. Blurton-Jones and colleagues will administer their stem cell therapy to mice that have been engineered to develop amyloid plaques and experience significant brain cell loss. The cognitive ability of these mice will be tested 1 month, 3 months and 6 months after treatment. Finally, the researchers will measure their animals' beta-amyloid and brain cell levels. Dr. Blurton-Jones' team hopes this effort will lead to a more comprehensive stem cell treatment, one that can slow not only the cognitive decline but also the underlying structural brain damage of Alzheimer's disease.