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 memory-robbing 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 analyze two of the nation's largest health insurance databases 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."
Preventing Alzheimer's
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 U.S. 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 analyzed 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," they report in a new scientific paper.
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.
If successful, the benefits could be tremendous, as Alzheimer's rates are climbing dramatically. Nearly 7 million Americans are living with Alzheimer's today, but that number is expected to climb to 13 million by 2050. Further, the estimated annual cost of care for Alzheimer's and other dementias could rise from $360 billion to almost $1 trillion, the Alzheimer's Association reports.
"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."
Findings Published
The researchers have published their findings in Alzheimer's & Dementia: The Journal of the Alzheimer's Association. The research team consisted of Joseph Magagnoli, Meenakshi Ambati, Tammy Cummings, Joseph Nguyen, Claire C. Thomas, Vidya L. Ambati, S. Scott Sutton, Bradley D. Gelfand and Jayakrishna Ambati. Jayakrishna Ambati is the co-founder of iVeena Holdings, iVeena Delivery Systems and Inflammasome Therapeutics; a full list of the authors' disclosures is included in the paper.
The research was supported by the UVA Strategic Investment Fund, grant 167; the National Institutes of Health, grants R01EY028027, R01EY029799, R01EY031039, R01AG078892, R01AG082108, R01EY028027, R01EY031039, R01AG078892, R01AG082108, R01EY032512 and R01DA054992; the DuPont Guerry III Professorship; and Mr. and Mrs. Eli W. Tullis.
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