Drs. Mike McDonald, Francesca-Fang Liao Receive $1 Million to Study Possible Alzheimer’s Therapy

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Francesca-Fang Liao, PhD, and Mike McDonald, PhD, of UTHSC received $1 million for a study that may have implications for Alzheimer’s disease in humans.

Researchers at the University of Tennessee Health Science Center (UTHSC) have received a $1 million grant to study a genetic therapy that one day may offer a way to slow or reverse the effects of Alzheimer’s disease.

Mike McDonald, PhD, an associate professor in the Departments of Neurology and Anatomy and Neurobiology, and Francesca-Fang Liao, PhD, a professor in the Department of Pharmacology, received the grant from the National Institute of Neurological Disorders and Stroke, a division of the National Institutes of Health, to test the therapy in mice. The funds will be distributed over three years.

Dr. McDonald said the therapy involves a single injection of a viral vector in the leg muscle. The vector, or carrier, contains DNA to generate a mutant erythropoietin. Erythropoietin, he said, or Epo, is a naturally occurring protein that is known to be neuro-protective, meaning it can protect neurons from damage in conditions such as Alzheimer’s and Parkinson’s diseases, macular degeneration and more. However, chronic use of Epo has the effect of raising hematocrit, the concentration of red blood cells, to unhealthy levels.

“But what we’re studying is a mutant Epo, with just one amino acid different,” Dr. McDonald said. “It does not raise the hematocrit, but continues to protect the neurons.” This modified Epo vector – rAAV.EpoR76E – was created by Tonia Rex, PhD, a former UTHSC faculty member.

“The nice thing is that it’s just a single intramuscular injection,” he continued. “We inject the virus, and the virus makes the protein – the mutant protein – forever. It gets into the bloodstream, then it gets into the brain, and there it does its work.”

In addition to protecting neurons, rAAV.EpoR76E clears the amyloid plaques, or sticky buildup outside nerve cells or neurons, associated with Alzheimer’s disease. Preliminary data show that amyloid plaques are nearly completely cleared two months after a single injection in mice that had extensive plaques in the cortex and hippocampus. Successfully reducing amyloid plaques and the resulting cell death, memory impairment and behavioral changes in mice may provide insight into new treatment strategies for humans with Alzheimer’s disease.