Nucleoside Reverse Transcriptase Inhibitors May Slow the Development of Alzheimer's Disease
Nucleoside reverse transcriptase inhibitors (NTRIs) were developed to treat HIV infection, interfering in the ability of the virus to replicate. Researchers here present epidemiological evidence for this class of drug to slow the onset of Alzheimer's disease. The researchers focus on reduced inflammation as a driving mechanism, but it seems plausible that this outcome occurs because NTRI's interfere in harmful transposable element activities. Transposable elements such as retrotransposons are largely the genetic remnants of ancient viral infections. They make up a sizable fraction of the genome. These sequences are suppressed in youth, but with age and the epigenetic changes characteristic of aging, transposable elements become active, duplicate themselves in the genome to cause mutational damage, create particles that sufficiently resemble viruses to trigger innate immune responses, and cause other harms.
NRTIs, or nucleoside reverse transcriptase inhibitors, are used to prevent the HIV virus from replicating inside the body. Researchers 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 researchers 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." 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.