HIV drugs offer substantial Alzheimer’s protection, study finds

Alzheimer’s disease stands as the most widespread form of dementia globally, increasingly burdening families, healthcare systems, and societies as populations age. Although current treatments, including acetylcholinesterase and amyloid-beta (Aβ) inhibitors, offer some relief, they don't effectively halt disease progression.

Now, researchers from UVA Health have uncovered a promising link between drugs initially developed for HIV and reduced Alzheimer's risk, highlighting an unexpected pathway for potential prevention.

The progression of Alzheimer’s involves complex mechanisms in your brain. Harmful protein formations like Aβ oligomers and hyperphosphorylated tau fibrils trigger inflammation, contributing significantly to cognitive decline. A protein complex called the NLRP3 inflammasome activates in response to these harmful proteins, causing inflammation and cell death. This reaction creates a harmful cycle, reinforcing further protein buildup and brain damage.

Researchers recognized that controlling the NLRP3 inflammasome might slow or prevent Alzheimer’s. Previously, Dr. Jayakrishna Ambati and his team at UVA Health found that nucleoside reverse transcriptase inhibitors (NRTIs), drugs already FDA-approved for treating HIV and hepatitis B, could suppress inflammasome activity beyond their original antiviral role. Independent studies confirmed these findings, suggesting broader medical applications for these drugs.

Given this discovery, Ambati and his colleagues sought to test whether these drugs could lower Alzheimer’s risk in humans. They reviewed massive health insurance databases, specifically looking at patients aged 50 and older who took NRTIs for HIV or hepatitis B. Over a span of 24 years, they examined records from the U.S. Veterans Health Administration database and MarketScan, a database representing a wider demographic.

The findings were significant. Individuals who took NRTIs consistently had a noticeably lower risk of developing Alzheimer’s. In the veterans' database, each year on these drugs correlated with a 6% lower chance of Alzheimer's, while the MarketScan data showed an even more dramatic 13% annual risk reduction.

Ambati highlighted the scale of this discovery: “It’s estimated that over 10 million people around the world develop Alzheimer’s disease annually. Our results suggest that taking these drugs could prevent approximately 1 million new cases of Alzheimer’s disease every year.”

The connection between HIV drugs and Alzheimer’s wasn't accidental. Ambati’s team originally identified that NRTIs blocked inflammasome activation—a known player in Alzheimer’s—independent of their ability to treat HIV. This key observation was vital, as no other types of HIV medications showed a similar protective effect. Thus, inflammasome-blocking appears uniquely beneficial.

Previous research had already shown inflammasome inhibition provided protection in various conditions, including diabetes-related eye diseases and age-related macular degeneration (AMD). Indeed, people using NRTIs had a reduced risk of AMD, a disease sharing similar inflammatory pathways with Alzheimer's. These insights strengthened confidence in the hypothesis linking NRTIs to Alzheimer's prevention.

Encouraged by these robust findings, Ambati and his team advocate launching clinical trials to formally test NRTIs as preventative treatments for Alzheimer’s. The need for such therapies grows urgent, given current projections. Alzheimer’s affects nearly 7 million Americans today, with that figure expected to nearly double by 2050. Consequently, the economic burden of caring for Alzheimer's patients could escalate dramatically, potentially nearing $1 trillion annually.

Additionally, Ambati’s group has developed K9, a newer drug specifically targeting inflammasome activity more safely and effectively than traditional NRTIs. Clinical trials for K9 are already underway for other inflammatory diseases, and the team plans to extend these trials to Alzheimer's.

“This drug is already in clinical trials for other diseases, and we plan to also test K9 in Alzheimer’s disease,” said Ambati. If these trials prove successful, the drug could offer a groundbreaking method to prevent Alzheimer’s, substantially altering the course of this devastating disease.

The implications are profound. Targeting inflammation through inflammasome inhibition might revolutionize Alzheimer’s prevention, offering hope to millions worldwide. The discovery aligns with a broader trend toward exploring inflammation's role in neurological diseases, highlighting how treatments for one disease can unexpectedly benefit another.

Ultimately, Ambati's research underscores the critical need for new perspectives in combating Alzheimer's, moving beyond traditional drug targets. By repurposing established HIV medications, researchers might rapidly deliver new, effective treatments to those at risk, significantly impacting global health.

Research findings are available online in the journal Alzheimer s & Dementia.

Note: The article above provided above by The Brighter Side of News.

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