Scientists Focus on Brain Challenges Linked to HIV
The University of Rochester Medical Center (URMC) is at the forefront of a significant project aimed at developing the world's first treatment for preventing or easing the neurological effects of HIV. This research, funded by the National Institute of Mental Health, is focused on understanding cognitive impairment in people living with HIV and developing interventions to improve treatment adherence and neurocognitive outcomes.
The project's team includes scientists from URMC, the University of Nebraska, and biotech company Califia Bio Inc. Notable members include Sanjay Maggirwar, Ph.D., associate professor of Microbiology and Immunology, Stephen Dewhurst, Ph.D., professor of Microbiology and Immunology, and Hulin Wu, Ph.D., professor of Biostatistics and Computational Biology, all from URMC. Howard Gendelman, M.D., heads the Center for Neurovirology and Neurodegenerative Disorders at the University of Nebraska Medical Center and is working closely with Gelbard's group. Michael Boska, Howard Fox, Larisa Poluektova, and others from the University of Nebraska Medical Center, Val Goodfellow, and Colin Loweth from Califia Bio Inc., are also part of the team.
The team's strategy involves identifying cognitive deficits, particularly executive function, in HIV-positive individuals, especially children and adolescents. They aim to address mental health challenges related to HIV and antiretroviral therapy (ART), including neuropsychiatric symptoms and adherence barriers. Advanced neuroimaging, multimodal assessments, and emerging technologies such as virtual reality and machine learning are being utilised to decode neural dysfunction and symptom progression, potentially enabling targeted interventions.
The team has created a test compound that shows promise in the laboratory. This compound, designed to slow or eliminate inflammation by knocking out an enzyme known as MLK3, has demonstrated the ability to reduce inflammation dramatically and preserve the structure of synapses, which are central to brain cell communication and especially vulnerable to damage caused by HIV in the brain.
Despite antiretroviral combination therapy (cART) lowering HIV levels in the body to a thousandth or less of what it would otherwise be, extending healthy life for many HIV patients, an assault triggered by HIV continues in the brain, causing HIV-associated neurocognitive disorder (HAND) in about half of patients. Symptoms of HAND include difficulty thinking or concentrating. So far, no drug has been identified to treat HAND in studies on people.
The project recently received $6.7 million in new funding from the National Institute of Mental Health, with plans to apply for further funding to fast-track the development of the compound into a drug that can be tested in patients. The team plans to begin a clinical trial in people within five years.
URMC's research on HAND also includes the HANDZ study, which examines executive function and adherence in children and adolescents living with HIV, partly located in Zambia. This study aims to characterise neurocognitive impairment related to HIV in pediatric populations and its impact on adherence to antiretroviral therapy (ART), which is crucial since cognitive dysfunction can worsen treatment compliance and quality of life. URMC's neurological experts collaborate internationally to assess these impairments using clinical neuropsychological measures to identify deficits and inform treatment development.
In summary, URMC's research progress on HIV-associated neurocognitive disorder involves multidisciplinary, international clinical studies focused on cognitive function and adherence, paired with neuroscience and technological innovations to develop future therapeutic strategies supported by National Institute of Mental Health funding.
- The research at the University of Rochester Medical Center (URMC) is not only focused on developing a treatment for preventing or easing the neurological effects of HIV, but also on understanding cognitive impairment in people living with HIV, particularly in children and adolescents, as part of their broader study on HIV-associated neurocognitive disorder (HAND).
- The project's strategy includes addressing mental health challenges related to HIV and antiretroviral therapy (ART), such as neuropsychiatric symptoms and adherence barriers, utilizing advanced neuroimaging, multimodal assessments, and emerging technologies like virtual reality and machine learning to decode neural dysfunction and symptom progression, potentially leading to targeted interventions for various medical-conditions like mental-health issues and neurological-disorders.
