Common HIV drugs are associated with reduced risk of Alzheimer's disease

Alzheimer's disease (AD) currently affects approximately 7 million people in the United States. This number is expected to increase to nearly 13 million by 2050, and the lack of meaningful treatment represents a major unmet medical need. Sanford Burnham Prebys scientists have now identified a promising real-world link between a common HIV treatment and lower rates of Alzheimer's disease. The study, led by Jerrold Chun, M.D., pharmaceuticals.

Chun's new research builds on his lab's landmark publication. Nature In 2018, he described how somatic gene recombination in neurons creates thousands of new gene variants in Alzheimer's disease brains. Importantly, they also show for the first time how APP, a gene associated with Alzheimer's disease, is recombined using the same type of enzyme found in HIV.

This enzyme, called reverse transcriptase (RT), can copy an RNA molecule, change it into a complementary DNA copy, and then insert it back into the DNA, making permanent sequence changes within the cell's DNA blueprint. cause.

HIV and many other viruses rely on RT to hijack host cells and establish chronic infections. Drugs that block the activity of RT enzymes have therefore become a common part of therapeutic cocktails to keep HIV at bay.

The brain appears to have its own RT, distinct from the virus, and the research team wondered whether blocking the brain's RT with HIV drugs would actually help Alzheimer's patients.

To assess the association between real-world RT inhibitor exposure and Alzheimer's disease in humans, the team analyzed de-identified medical records containing prescription claims from more than 225,000 control patients and HIV-positive patients. We found that RT inhibitor exposure was associated with a statistically significant reduction in incidence. and the prevalence of AD.

So we looked at HIV-positive people who were taking RT inhibitors and other antiretroviral combinations as they aged, and asked the question: How many of them developed Alzheimer's disease? And the answer is that compared to the general population, there are far fewer than expected. ”

Jerrold Chun, MD

Of the more than 225,000 individuals with insurance claims data in the study, just under 80,000 were over the age of 60 and living with HIV. More than 46,000 people were taking RT inhibitors during the nearly three-year observation period from 2016 to 2019. Data This information was obtained through a collaboration with IQVIA, a medical information technology and clinical research company led by Tiffany Chou, MD.

Among living HIV-infected people, 2.46 per 1,000 people with HIV taking these inhibitors were diagnosed with Alzheimer's disease, compared with 6.15 in the general population. This control group included more than 150,000 of her HIV-negative patients over the age of 60 who had medical insurance claims related to cold treatment.

“It would be impractical to conduct a prospective clinical trial with this number of patients,” Chun added. “This approach is a way to study how drugs work in large patient populations.”

Chun said the drugs taken by patients in this retrospective study were designed to counteract the RT activity of HIV and had limited effects on the many different forms of the enzyme that are active in the brain. It emphasizes that there is a high possibility that

“What we're looking at right now is very crude,” Chun said. “The obvious next step for our lab is to identify which version of RT is at work in the Alzheimer's brain so that we can discover more targeted treatments, while Prospective clinical trials of currently available RT inhibitors in patients with early-stage Alzheimer's disease should also be pursued.

Jerrold Chun, MD, is a professor in the Sanford Burnham Prebys Center for Genetic Disease and Aging Research.

Other authors of the study include Tiffany W. Chow, Mark Raupp, Matthew W. Reynolds, Siying Li, and Gwendolyn E. Kaeser.