Longevity Briefs: Will These Drugs Finally SToMP Alzheimer’s Disease?

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: What are the fundamental biological processes driving Alzheimer’s disease? We still don’t know for sure, but it’s hypothesised that senescent cells play a significant role. Senescent cells are dysfunctional cells that can no longer replicate, but also refuse to die. Alzheimer’s patients have more senescent cells in their brains than healthy people, particularly senescent microglia. Microglia are the ‘janitors’ of the brain, helping to keep it free of misfolded proteins that are thought to be a key component of Alzheimer’s disease. Senescent cells also promote inflammation – another key component of Alzheimer’s.

We already have clinically approved drugs that can destroy senescent cells (known as senolytics), but can they help Alzheimer’s patients where so many other drugs have failed?

What did the researchers do: In these early results from a clinical trial called SToMP-AD, participants with early symptomatic Alzheimer’s disease were given dasatinib and quercetin, a well studied senolytic drug combination. Dasatinib is an approved anti-cancer drug, while quercetin is a plant compound with anti-inflammatory properties. Treatment lasted 12 weeks and has so far been completed by 5 participants. It was an open label study, meaning that both patients and professionals administering the drugs were aware of what drugs were being given. It was published in preprint and has not yet completed peer review.

Key takeaway(s) from this research:

• The treatment was relatively safe and was shown to reach the brain
• Participants experienced a reduction in inflammation but this was not statistically significant due to the small size of the study
• Treatment did not appear to improve cognitive function, perhaps due to insufficient doses

While there aren’t many firm conclusions to be drawn from such a small trial, this does represent some of the very first evidence we have for the effects of senolytics on Alzheimer’s disease in humans. This is a very exploratory study with the main goal of investigating safety and verifying that the treatment is able to reach the brain. In this respect the results are encouraging, with few adverse effects reported and confirmation that the treatment reaches the central nervous system.

The researchers detected a reduction in markers of inflammation, which would be expected for a treatment that targeted senescent cells. However, because very few people have so far completed the trial, they were not able to show that this change was statistically significant. They also did not see any improvement in cognitive function among participants.

If senescence was a really important cause of Alzheimer’s, one might have hoped for more impressive results, even with such a small number of patients. Still, the doses used in this trial were quite conservative. Other trials are underway with larger doses, but no results have been published yet.