URMC Neurologist Receives International Neurovirology Award

Sep. 7, 2016

Harris Harris “Handy” Gelbard, M.D., Ph.D., director of the Center for Neural Development & Disease at URMC, is slated to receive the Hilary Koprowski Prize in Neurovirology at this year’s International Symposium on Molecular Medicine and Infectious Disease at Drexel University. Gelbard will be recognized for developing an unconventional drug that shows promise in treating brain disorders associated with HIV. 

Gelbard’s drug, URMC-099, calms the immune system when it goes awry, as happens in HIV Associated Neurocognitive Disorder (HAND).  In HAND, immune reactions to HIV particles in the brain damage nerve cells and cause dementia. Because patients affected by HAND also have HIV, it was imperative that URMC-099 not interfere with the antiretroviral drugs that keep HIV-positive patients alive.

Surprisingly, when tested in mice, URMC-099 boosted the concentration of a nanoformulated antiretroviral drug, and prolonged its effect, essentially turning the cells into “drug factories”. The cells began packaging the drug and sending it out to neighboring cells. Gelbard hopes that URMC-099 could make antiretroviral drugs last longer in humans as well –making it possible to reduce the frequency of dosing and increasing compliance.

The “selectively non-selective” aspect of URMC-099 is what makes it unconventional – and effective. Targeting a single molecule at a time is standard pharmaceutical practice that minimizes the risk of drug side effects. URMC-099 targets several molecules at once that are associated with Mixed Lineage Kinases (MLKs), which act like railroad switches in cellular pathways that control stress responses and package viruses.

“I don't eschew the importance of keeping off target effects in mind,” said Gelbard, “but disease is almost never a single target. We are too complicated.”

URMC-099, and its non-selective nature, beats its selective drug competitors at restoring health in mouse models of Multiple Sclerosis (MS), an autoimmune neurodegenerative disease, and Non-Alcoholic Fatty Liver Disease, a high fat and sugar diet induced damage to the liver.

Graphic of infected brain

Not only does this highlight the fact that the unpopular tactic of non-selectivity may be necessary in treating certain diseases, but it also demonstrates the broad applications for this drug. Though URMC-099 has not yet been tested in humans, it shows great promise for both infectious and non-infectious diseases.

That is why Drexel University’s Institute of Molecular Medicine and Infectious Disease selected Gelbard to receive the Hilary Koprowski prize, named for a world-renowned biomedical researcher.

“I'm hugely flattered to receive this award,” said Gelbard. “This puts me in august company.  Hilary Koprowski probably should have gotten a Nobel Prize.”

Koprowski developed the first successful polio vaccine – a live vaccine that was utilized effectively abroad, but was never approved for use in the US. His vaccine was soon eclipsed by those of Jonas Salk and Albert Sabin. Instead, Koprowski gained notoriety for developing a better, less painful rabies vaccine that is used to this day. 

Gelbard also recently received the inaugural award of the Translational Research in NeuroVirology Lectureship at the International Society for Neurovirology meetings in 2015.


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