Scientists Focus on Solving Cognitive Challenges Linked to HIV
University of Rochester Leads the Way in Developing First Treatment for HIV's Neurological Effects
In a significant breakthrough, a team of scientists and doctors, including those from the University of Rochester Medical Center, University of Nebraska, and biotech company Califia Bio Inc., are working to develop the world's first treatment for the neurological effects of HIV.
The project, which received $6.7 million in new funding from the National Institute of Mental Health, aims to address HIV-associated neurocognitive disorder (HAND), a condition for which no drug has yet been identified. HAND affects about half of HIV patients, causing symptoms such as difficulty thinking or concentrating due to the effects of HIV on the brain.
The team has created a compound that shows promise in laboratory tests. The test compound is designed to slow or eliminate inflammation by knocking out an enzyme known as MLK3. MLK3 plays a key role in the inflammatory process that causes damage in the brain due to HIV.
In tests, the compound has reduced inflammation dramatically and has preserved the structure of synapses, which are central to the ability of brain cells to communicate with each other. The lead compound successfully gets into the brain and stays there at levels necessary to knock out MLK3.
The success of combination antiretroviral therapy (cART) does not extend fully to the brain, where HIV continues to cause damage. cART can lower virus levels in the body to a thousandth or less of what it would otherwise be, but the virus still finds its way into the brain, causing ongoing damage.
The team plans to begin a clinical trial in people within five years. Before that, they plan to apply to the National Institutes of Health for funding to fast-track the development of the compound into a drug that can be tested in patients.
The team used clues from a failed study on an experimental drug for Parkinson's disease to improve their compound for targeting MLK3. When MLK3 is abnormally active, it prompts cells that normally nourish the brain's neurons to attack them and synapses.
Howard Gendelman, M.D., who heads the Center for Neurovirology and Neurodegenerative Disorders at the University of Nebraska Medical Center, is working closely with Gelbard's group. Other key members of the team at the University of Rochester Medical Center include Stephen Dewhurst, Ph.D., professor of Microbiology and Immunology, Sanjay Maggirwar, Ph.D., associate professor of Microbiology and Immunology, and Hulin Wu, Ph.D., professor of Biostatistics and Computational Biology.
Gelbard notes that progress against HIV-related dementia is likely to pay off for other conditions as well, such as Alzheimer's and Parkinson's diseases, and heart failure. The team's work could pave the way for new treatments for a wide range of neurological disorders.
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