Could HIV drugs help fight this condition?

Chun explained that his and his team’s study is based on previous research published in 2018 that identified a reverse transcriptase-dependent phenomenon called “somatic gene recombination,” which affected genes capable of promoting Alzheimer’s disease.

“Reverse transcriptase is a famous protein — a protein that can do things is called an ‘enzyme’ and reverse transcriptase is an enzyme — that can copy RNA — the stuff that encodes proteins in our cells — back into DNA, a ‘reverse’ process from the usual ‘Central Dogma’ of DNA-to-RNA-to-protein.”

– Jerold Chun, MD, PhD

“The reverse transcriptase was and is thought to be part of our brain — i.e., endogenous vs. from an exogenous viral infection,” he continued. “This [previous] discovery raised the possibility that blocking reverse transcriptase might be helpful in treating Alzheimer’s disease.”

Chun said that reverse transcriptase was first discovered in RNA viruses in 1970.

“It turns out that our brain — and body — have their own reverse transcriptases, which may go awry to promote Alzheimer’s disease and likely other brain disorders,” he detailed.

“HIV — the virus that causes AIDS — itself is an RNA virus that has its own reverse transcriptase. Medical science and the pharmaceutical industry have discovered many drugs called reverse transcriptase inhibitors that interrupt HIV’s life cycle, which has saved many AIDS patients,“ Chun said.

“Some of these same drugs could also work on the brain’s reverse transcriptases, which we examined observationally in the current study in those aged survivors who had received reverse transcriptase inhibitors,” he added.

For this study, Chun and his team analyzed medical records from more than 225,000 people, with about 80,000 having HIV and over the age of 60. More than 46,000 study participants had taken reverse transcriptase inhibitors.

Upon analysis, the researchers found that study participants who had exposure to reverse transcriptase inhibitors had a statistically significant reduced occurrence and frequency of Alzheimer’s disease.

“These results were expected,” Chun said. “In our 2018 report, we searched for cases of HIV-positive persons with Alzheimer’s disease and really could not find robust evidence of them, despite an expectation a decade earlier by some in the HIV field, of an avalanche of Alzheimer’s disease patients coming from this group.”

“Instead, [the] first apparent case was only seen in 2016,” he continued. “We, therefore, pursued an in-depth look by assessing tens of thousands of medical records of appropriate patients and controls, resulting in the current report that identified beneficial effects of reverse transcriptase inhibitor exposure in reducing Alzheimer’s disease.”

Chun also cautioned that more research is still needed to examine the medicine and science of reverse transcriptases in Alzheimer’s disease and other brain diseases:

“Prospective clinical trials using reverse transcriptase inhibitors to reduce Alzheimer’s disease are warranted in light of our study and the accumulating scientific literature, and questions remain on when such drugs could work best in Alzheimer’s disease, on whether there are certain Alzheimer’s disease sub-populations who could most benefit, and whether certain drugs work better than others, which we believe is the case.”

He explained that some questions we need to ask are: “Scientifically, what is the source of endogenous [brain] reverse transcriptases; what cells use it normally and what does it do there; and how/where/when might it go awry?”

“Knowing this could enable the development of better Alzheimer’s disease therapeutics, as well as extensions into other brain diseases,” Chun noted.

“Finally, appropriate reverse transcriptase inhibitors are already FDA-approved for treating HIV — and hepatitis B — meaning that they could be prescribed to appropriate Alzheimer’s disease patients now, as clinical trials that take many years are pursued. This may be especially helpful in countries that use generic drugs since a number of reverse transcriptase inhibitors are generic, towards helping Alzheimer’s disease patients and their families,” the researcher suggested.

After reviewing this research, Karen D. Sullivan, PhD, ABPP, a board-certified neuropsychologist, owner of I CARE FOR YOUR BRAIN, and Reid Healthcare Transformation Fellow at FirstHealth of the Carolinas in Pinehurst, NC, told MNT she found it to be an intriguing and impressive study.

“With a difference of 2.46 Alzheimer’s disease diagnoses per 1,000 persons among HIV-positive individuals taking reverse transcriptase inhibitors versus 6.15 for the general population, there is clearly an effect of this compound,” Sullivan noted.

“Our current treatment options for Alzheimer’s disease only reduce decline to a modest degree with no prevention or reversal possible. We need to invest in novel approaches, like this one, to find the next generation of options,” she continued.

MNT also spoke with Manisha Parulekar, MD, director of the Division of Geriatrics at Hackensack University Medical Center, and co-director of the Center for Memory Loss and Brain Health and associate professor at Hackensack Meridian School of Medicine in New Jersey, about this study.

“Studies have shown elevated levels of reverse transcriptase activity in the brains of individuals with Alzheimer’s disease compared to healthy individuals, suggesting a possible association,” Parulekar said.

“Few studies have also explored possible correlation with tau protein and inflammation. Reverse transcriptase is an enzyme that plays a complex and not completely understood role in Alzheimer’s disease. While its exact contribution remains under investigation, several studies, including this new study, suggest a potential link between reverse transcriptase activity and the development of Alzheimer’s disease.”

– Manisha Parulekar, MD

“We do need to establish [a] better understanding of the correlation of reverse transcriptase and Alzheimer’s disease pathology,” she added. “This will allow us to get to the next steps of effective treatment options.”