TMARC Pilot Studies - Completed

Association of Free Mitochondrial DNA & Mitochondrial Genetic Defects with Neurological Damage & Neurocognitive Decline During HIV Infection & METH Use (Pérez-Santiago)

Agency: TMARC
PI: Pérez-Santiago, Josue, Ph.D.


During HIV infection, inflammation within the central nervous system (CNS) can result in neurologic damage and neurocognitive impairment.  The use of methamphetamine can also cause neurological dysfunction, which is likely compounded in HIV infection. The mechanisms underlying these interacting phenomena remain unclear. One possible mechanism that is shared by HIV infection, HIV antiretroviral therapy, and methamphetamine use is mitochondrial damage within the CNS. The level of damage may be assessed by quantifying the presence of the mitochondrial “common deletion”, an acquired defect associated with neurodegenerative diseases, mitochondrial toxicity from medications, substance abuse, and general aging.   In this proposed study, we will determine the relative presence of the mitochondria carrying the “common deletion” and how the presence of this “common deletion” is directly associated with neurological damage and subsequently neurocognitive decline during HIV infection and methamphetamine abuse. Additionally, we will determine the association between the levels of free mitochondrial DNA in cerebrospinal fluid (CSF), which is a marker of cellular damage, with neurological pathology. To this end, we plan to quantify mitochondrial number as well as the number of mitochondria carrying the “common deletion” using the highly sensitive and precise droplet digital PCR platform from HIV-infected individuals with and without methamphetamine use and HIV-uninfected controls.  This study will provide a better understanding of the role of mitochondrial genetic defects on neurocognitive performance, which might lead to better therapeutic interventions in the context of HIV. We also expect to validate this novel biomarker of neurological damage in a more accessible source, i.e. CSF vs. brain tissue.

Sponsored by NIH/NIDA P50DA026306

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