Working on a grant of up to $22 million in collaboration with University of Rochester researchers, Brown researchers will investigate whether a drug originally developed to treat HIV can slow human aging — the culprit of inflammation that causes diseases like cancer and Alzheimer’s. The grant, from the Advanced Research Projects Agency for Health, will support clinical trials in humans.
Led by John Sedivy — Center on the Biology of Aging director and professor of biology — and Vera Gorbunova — Rochester Aging Research Center co-director and professor of biology at the University of Rochester — the grant will help the team investigate how the HIV drug Censavudine can reduce the inflammatory effects of retrotransposons.
Sedivy explained that the researchers use HIV drugs because the retrotransposons are “genetically related” to the disease.
Retrotransposons become more active as the host ages. according to Sedivy, these virus-like mobile segments of DNA are sometimes called “jumping genes” and integrate into different locations in the host genome. In addition, they cause inflammation that contributes to age-related diseases like Alzheimer’s and ALS.
Because retrotransposons use a similar pathway as HIV to replicate and integrate into host genomes, drugs developed to treat HIV by inhibiting reverse transcriptase — the enzyme that enables that replication cycle — have been able to control retrotransposons as well. In the past, Sedivy and Gorbunova have found that HIV drugs mitigate retrotransposon-related inflammation.
There are already many FDA-approved drugs for HIV that the researchers have tested on Alzheimer’s in the past — first on mice and then in relatively smaller clinical studies. The $22 million grant will support a “much bigger” study on a “new generation of reverse transcriptase inhibitors.”
This new drug is more potent and has fewer side effects, according to Maxfield Kelsey GS and Ethan Grant GS, who are Ph.D. candidates in Sedivy’s lab.
“The mechanism is cellular, but the effect is whole body,” Grant said.
If the drug is found to slow aging in mice, the study will move on to human patients in a clinical trial in approximately two years, Gorbunova wrote in an email to The Herald.
“What’s really kind of crazy is that I really think this would be the first drug that would be shown to slow human aging, if successful,” Kelsey said. In the clinical trial, researchers will look for biomarkers of aging to assess how well the drug is working, according to Kelsey.
This research is significant because “we’re all aging, and we’re all going to get diseases of aging if we make it that far,” Grant said.
Sedivy said that retrotransposons are “really fundamental core mechanism(s) of aging,” so “the key here is to slow things down” more upstream.
“This will slow down many diseases at the same time, so you don’t have to target each disease with its own pill,” Sedivy said.
According to Gorbunova, this work has the potential to “improve health and wellbeing of millions of people.”
“We urgently need to find ways to make older people healthier so they stay active for (a) longer time, enjoy life and take care of themselves,” Gorbunova wrote. “This will not only alleviate human suffering but will have a tremendous beneficial impact on … society.”
Elizabeth Rosenbaum is a senior staff writer covering science and research.
