Research Shows Diabetes Drug Improves Memory

DOUBLE DUTY—Larry Denner, Ph.D., and Kelly Dineley, Ph.D., researchers at the University of Texas Medical Branch at Galveston, found that the drug Avandia not only treats insulin resistance, but also enhances learning and memory.

By Molly Dannenmaier  |  UTMB at Galveston

An FDA-approved drug initially used to treat insulin resistance in diabetics has shown promise as a way to improve cognitive performance in some people with Alzheimer’s disease.

Working with genetically engineered mice designed to serve as models for Alzheimer’s, University of Texas Medical Branch at Galveston researchers found that treatment with the anti-insulin-resistance drug Avandia enhanced learning and memory as well as normalized insulin resistance. The scientists believe the drug produced this response by reducing the negative influence of Alzheimer’s on the behavior of a key brain-signaling molecule.
 
The molecule, called extracellular signal-regulated kinase, or ERK, becomes hyperactive both in the brains of Alzheimer’s patients and in mice that have a disease state that corresponds to mild cognitive impairment in human Alzheimer’s. This excessive molecular activity disrupts communication among nerve cells, interfering with learning and memory.

Avandia, whose scientific name is Rosiglitazone, brings ERK back into line.

“Using this drug appears to restore the signaling between neurons that is required for proper cognitive function,” said UTMB professor Larry Denner, Ph.D., the lead author of the paper published in the Nov. 21 edition of the Journal of Neuroscience. “It gives us an opportunity to test several FDA-approved drugs to normalize insulin resistance in Alzheimer’s patients and possibly also enhance memory, and it also gives us a remarkable tool to use in animal models to understand the molecular mechanisms that underlie cognitive issues in Alzheimer’s.”

ERK dysfunction in the Alzheimer’s mice was discovered several years ago by UTMB associate professor Kelly Dineley, Ph.D., senior author of the Journal of Neuroscience paper. But connecting the protein, the insulin resistance drug and memory is a new development.

Now the UTMB research team and other investigators across the world are starting clinical trials to investigate the value of therapies for insulin resistance in early-stage Alzheimer’s disease in humans.