2010 Grants - Tenner

C5a Receptor as a Target to Slow Progression of Alzheimer's Disease

Andrea Joan Tenner, Ph.D.
University of California, Irvine
Irvine, California

2010 Investigator-Initiated Research Grant

Alzheimer's disease is associated with numerous changes in the brain, including inflammation and activation of some immune responses. One immune response leads to generation of a protein fragment known as C5a. In turn, C5a activates receptors on the surface of supporting cells in the brain, triggering activity that promotes the development of Alzheimer pathology.

Using mice that have been genetically altered to express Alzheimer-like pathology, Andrea Joan Tenner, Ph.D., and colleagues have found that an inhibitor of C5a prevents Alzheimer-like pathology and improves brain function. The researchers plan to extend their studies to determine if this C5a inhibitor, known as PMX205, is a good candidate for studies in humans. They plan to assess whether PMX205 can reverse brain pathology as well as prevent it, whether the drug enters the brain, and whether its beneficial effects require entry to the brain or occur elsewhere in the body. Preliminary evidence suggests that PMX205 has few side effects, but the researchers will also study this aspect of the drug. These studies will lay the foundation for possible trials of PMX205 or a closely related drug in humans with early-stage Alzheimer's disease.