HIV drugs show promise against Alzheimer’s disease

A class of medications commonly used to treat HIV and hepatitis B could offer an unexpected benefit: protection against Alzheimer’s disease.

In a study published on May 8 in Alzheimer’s and dementiaResearchers of the Health System of the University of Virginia have discovered convincing evidence that nucleoside transcriptase inhibitors (NRTI) significantly reduce the risk of developing Alzheimer’s disease. The study, which analyzed health records of more than 270,000 patients in two main US health insurance databases. These findings could transform prevention strategies for a disease that affects millions worldwide and has proven stubbornly resistant to effective treatments.

The discovery offers a new hope in the challenging field of Alzheimer’s research, where many promising treatments have failed in the late clinical trials.

Beyond HIV treatment: a new purpose for established medicines

The Nrti have been a cornerstone of HIV treatment for decades, working by preventing the virus from replicating inside the body. However, researchers have discovered that these medications have another valuable property: they inhibit inflammoms, protein complexes that play a crucial role in the body’s immune response.

Dr. Jayakrishna Ambati, founding director of the Center for Advanced Vision of UVA and principal researcher in the study, had previously identified this mechanism. His team suspected that it could be relevant to Alzheimer’s disease, where inflammation has been increasingly recognized as a key factor in the progression of the disease.

“It is estimated that more than 10 million people worldwide develop Alzheimer’s disease annually,” said Ambati. “Our results suggest that taking these medications could prevent approximately 1 million new cases of Alzheimer’s disease every year.”

Comprehensive analysis in various populations

The research team analyzed two main health insurance databases: the veteran health administration database, which mainly includes the major male veterans and the Marketscan database, which represents the commercially insured persons in a broader demographic spectrum.

To ensure that their findings were robust, the researchers implemented several methodological safeguards:

• Propensity behavior to minimize selection bias between NTTI users and non -users
• Adjusting almost 20 different medical conditions that affect Alzheimer’s risk
• Time -dependent analysis to take into account variations in drug exposure
• Competitive risk models to address the possibility that mortality differences can biased results
• Separate analysis for patients with HIV and those with hepatitis B to ensure that findings will not be limited to a single condition

Even after these rigorous controls, the protective effect remained clear and consisting of both databases. In the veteran health administration database, every year of Nrti treatment was associated with a reduced risk of 6% of developing Alzheimer’s. The effect was even stronger in the Marketscan database, with a reduction in the risk of 13% per year of treatment.

Inflammation: a key objective in Alzheimer’s disease

The study findings are aligned with the growing evidence that inflammation plays an important role in the development of Alzheimer’s disease. The inflammasoma NLRP3, a protein complex involved in the immune response, has been involved in the brain reaction to amyloid-base plates and in the tau entanglement, the distinctive physical characteristics of Alzheimer’s disease.

When these abnormal protein accumulations are produced, they can trigger inflameoma to launch an inflammatory response that finally contributes to neurodegeneration and cognitive deterioration. This creates a destructive cycle in which inflammation leads to a greater accumulation of proteins, which triggers greater inflammation.

The discovery of the research team suggests that by inhibiting the activation of inflameoma, Nrti can help break this cycle and protect against Alzheimer’s development.

Crucially, other types of HIV medications that do not inhibit inflammasomes, including NTTI, protease inhibitors and transfer chain transfer inhibitors, did not show the same protective effect, strengthening the case that the inhibition of inflammasoma is the key mechanism in work.

From database analysis up to clinical trials

While study findings are promising, researchers emphasize that database analysis cannot definitively establish causality. Clinical trials will be necessary to confirm the protective effect and determine optimal treatment approaches.

However, there are reasons for optimism. The small clinical trials of Nrti in Alzheimer’s disease are already underway, with a 24 -week pilot study of the Nrti Lamivudin that recently informs reductions in neurodegeneration and neuroinflammation biomarkers.

In addition, the grape team has developed a potentially superior option. “We have also developed a new inflammasome block medication called K9, which is a safer and more effective version of Nrti,” said Ambati. “This medicine is already in clinical trials for other diseases, and we also planned K9 in Alzheimer’s disease.”

K9 maintains the inhibitory properties of inflammasome of the Nrti while adding some of its limitations, such as the possible mitochondrial toxicity and the risk of developing viral resistance with long -term use. Preliminary tests in animal models have shown promising results, with the compound, according to reports, reverse space memory and learning impediments.

Significant implications for public health

The potential impact for the public health of these findings is substantial. With almost 7 million Americans who currently live with Alzheimer’s, a number that is projected that almost double to 13 million by 2050, effective prevention strategies could drastically reduce the human and economic cost of the disease. It is expected that Alzheimer’s annual cost only in the United States will increase from $ 360 billion to almost $ 1 billion in the middle of the century.

If clinical trials confirm the protective effect observed in this study, NRTI or their derivatives as K9 could represent a significant advance in Alzheimer’s prevention, particularly for high -risk individuals. The fact that these medications are already approved by the FDA for other conditions could accelerate its implementation for the prevention of Alzheimer’s, although dosing regimes and specific security profiles should be established for this new use.

As researchers continue to explore the connection between inflammasome inhibition and Alzheimer’s disease, this study adds substantial weight to the growing recognition that directed inflammation can represent one of the most promising pathways to combat this devastating condition.