UVA Health scientists are calling for clinical trials testing the potential of HIV drugs called NRTIs to prevent Alzheimer’s disease after discovering that patients taking the drugs are substantially less likely to develop the condition.
The researchers, led by UVA’s Jayakrishna Ambati, MD, previously identified a possible mechanism by which the drugs could prevent Alzheimer’s. That promising finding prompted them to analyse two of the largest health insurance databases in the US to evaluate Alzheimer’s risk among patients prescribed the medications. In one, the risk of developing Alzheimer’s decreased 6% every year the patients were taking the drugs. In the other, the annual decrease was 13%.
“It’s estimated that over 10 million people around the world develop Alzheimer’s disease annually,” said Ambati, founding director of UVA’s Center for Advanced Vision Science and the DuPont Guerry III Professor in the University of Virginia School of Medicine’s Department of Ophthalmology. “Our results suggest that taking these drugs could prevent approximately 1 million new cases of Alzheimer’s disease every year.”
NRTIs, or nucleoside reverse transcriptase inhibitors, are used to prevent the HIV virus from replicating inside the body. But Ambati and his team previously determined that the drugs can also prevent the activation of inflammasomes, important agents of our immune system. These proteins have been implicated in the development of Alzheimer’s disease, so Ambati and his colleagues wanted to see if patients taking the inflammasome-blocking drugs were less likely to develop Alzheimer’s.
To do that, they reviewed 24 years of patient data contained in the US Veterans Health Administration Database – made up heavily of men – and 14 years of data in the MarketScan database of commercially insured patients, which offers a broader representation of the population. They looked for patients who were at least 50 years old and were taking medications for either HIV or hepatitis B, another disease treated with NRTIs. They excluded patients with a previous Alzheimer’s diagnosis.
In total, the researchers identified more than 270,000 patients who met the study criteria and then analysed how many went on to develop Alzheimer’s. Even after adjusting for factors that might cloud the results, such as whether patients had pre-existing medical conditions, the researchers determined that the reduction in Alzheimer’s risk among patients on NRTIs was “significant and substantial".
The researchers note that patients taking other types of HIV medications did not show the same reduction in Alzheimer’s risk as those on NRTIs. Based on that, they say that NRTIs warrant clinical testing to determine their ability to ward off Alzheimer’s.
“We have also developed a new inflammasome-blocking drug called K9, which is a safer and more effective version of NRTIs,” Ambati said. “This drug is already in clinical trials for other diseases, and we plan to also test K9 in Alzheimer’s disease.”
The researchers have published their findings in Alzheimer's & Dementia: The Journal of the Alzheimer's Association.
