An HIV drug could treat Alzheimer's disease, says new study

Washington DC.: New study reveals that an anti-HIV drug significantly reduces age-related inflammation and other signs of aging in mice. The results were published Thursday, February 7 in the journal Nature. The collaborative research project included researchers from Brown, the University of New York, the University of Rochester, the University of Montreal and the Faculty of Medicine of the University. from Virginia.

Speaking about the study, John Sedivy said, "This is promising for the treatment of age-related disorders, including Alzheimer's disease," adding, "And not just Alzheimer's disease, but many other diseases: type 2 diabetes, Parkinson's disease, macular degeneration, arthritis, and so on. different things. It's our goal. "Age-related inflammation is an important component of age-related disorders."

Sedivy says the anti-HIV drug works by stopping the activity of retrotransposons in old cells. Retrotransposons – DNA sequences that can replicate and move to other places – are a substantial fraction of the human genome. Retrotransposons are related to old retroviruses that, when not controlled, can produce DNA copies of themselves that can be inserted into other parts of the genome. ;a cell.

The research team discovered that an important clbad of retrotransposons, called L1, can escape cell control and begin to replicate in both senescent human cells – old cells that no longer divide – and aged mice. The team tested six different HIV reverse transcriptase inhibitors to determine whether they could block L1 activity and the response to interferon. Lamivudine, a generic anti-HIV drug, is distinguished by its activity and low side effects.

The growth of human cells in the presence of lamivudine did not have an impact when cells reached senescence or killed senescent cells, Sedivy said. However, lamivudine decreased the response to interferon and the terminal senescence-badociated secretory phenotype (SASP) – the important features of senescent cells that promote inflammation in their neighbors.

"When we started giving this anti-HIV drug to mice, we found that they had these incredible anti-inflammatory effects," Sedivy said. "Our explanation is that although L1's are activated relatively late in senescence, the response to interferon enhances the response to SASP and is responsible for inflammation badociated with age."

The treatment of lamivudine in 26-month-old mice (approximately the 75-year-old equivalent of the male) for as little as two weeks reduced the interferon response signs. and inflammation, while treatment of mice aged 20 months to lamivudine for six months reduced signs of fat and muscle loss as well as kidney scarring.

Sedivy is eager to translate the results for humans. Specifically, he would like to begin clinical trials on lamivudine for various age-related conditions, such as frailty, Alzheimer's disease, and arthritis. Lamivudine was approved by the Food and Drug Administration in 1995, has been used to treat HIV / AIDS for decades, and its pharmacological activity and safety are well established, Sedivy said.

He would also like to develop a new reverse transcriptase inhibitor specifically for L1 reverse transcriptase. To help develop a specific treatment with minimal side effects, the molecular structure of L1 reverse transcriptase must be determined, he added. Researchers could also develop other types of drugs targeting L1 retrotransposons.