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Alzheimer's disease is a pressing concern as it affects nearly seven million people in the United States, with projections indicating a surge to nearly 13 million by 2050.

Addressing the shortage of effective therapies for Alzheimer's is a critical unmet medical need. Scientists at Sanford Burnham Prebys have unearthed significant real-world correlations between commonly used HIV medications and a diminished occurrence of the brain disorder.

Published in Pharmaceuticals, the study spearheaded by Jerold Chun, M.D., Ph.D., builds upon his team's groundbreaking 2018 revelation in Nature, explaining how somatic gene recombination in neurons generates numerous new gene variants within Alzheimer's-afflicted brains. Crucially, it unveiled the utilization of the same enzyme found in HIV, reverse transcriptase (RT), in the recombination of the Alzheimer's-associated gene, APP.

RT, a pivotal enzyme for HIV and various other viruses, initiates the development of chronic infections by copying RNA molecules and converting them into complementary DNA duplicates, which are then integrated back into the cell's DNA, causing permanent sequence alterations.

While HIV drugs impede RT activity to combat viral infection, the brain has its own RTs distinct from those in viruses. The research team hypothesized that inhibiting brain RTs with HIV medications could benefit Alzheimer's patients.

Analyzing anonymized medical records and prescription claims from over 225,000 control and HIV-positive patients, the team found a statistically significant reduction in Alzheimer's disease incidence and prevalence associated with RT inhibitor exposure.

"Thus, we looked at HIV-positive individuals taking RT inhibitors and other combined antiretroviral therapies as they aged, and asked the question: How many of them got Alzheimer's disease?" Chun said, according to Neuroscience News.

"And the answer is that there were many fewer than might have been expected compared to the general population."

The retrospective study revealed a noteworthy discrepancy in Alzheimer's diagnoses between HIV-positive individuals taking RT inhibitors and the general population, indicating a potential avenue for further research into Alzheimer's therapeutics.

Chun has emphasized the need for identifying specific forms of RTs active in the Alzheimer's-syricken brain for targeted treatment development, alongside advocating for prospective clinical trials investigating the efficacy of currently available RT inhibitors in individuals with early Alzheimer's.

"What we're looking at now is very crude," explained Chun. "The clear next step for our lab is to identify which versions of RTs are at work in the [Alzheimer's] brain so that more targeted treatments can be discovered, while prospective clinical trials of currently available RT inhibitors on persons with early [Alzheimer's] should be pursued."

Jerold Chun, M.D., Ph.D., holds a professorship in the Center for Genetic Disorders and Aging Research at Sanford Burnham Prebys. Additional authors of the study include Tiffany W. Chow, Mark Raupp, Matthew W. Reynolds, Siying Li, and Gwendolyn E. Kaeser.