An arthritis drug demos potential to help reverse Alzheimer's disease

Gladstone investigator Li Gan

A drug called salsalate, commonly used in treating rheumatoid arthritis, has been found to have beneficial effects in an animal model of Alzheimer's disease.

Gladstone Institute investigators Dr. Eric Verdin and Li Gan share authorship in the current study, which was published in Nature Medicine earlier this week.

Their work demonstrated that by inhibiting the toxic acetylation of the protein tau, they could prevent the accumulation of tau and consequently protect against the cognitive impairments in a mouse model of Alzheimer's disease and frontotemporal dementia (FTD).

There were three significant findings with the treatment of salsalate: the levels of tau protein were effectively reduced, memory impairments were accordingly improved, and degeneration of the hippocampus--an area of the brain key for memory formation and a hallmark feature in dementia patients--was not seen in treated mice.

"We identified for the first time a pharmacological approach that reverses all aspects of tau toxicity," said Li Gan. "Remarkably, the profound protective effects of salsalate were achieved even though it was administered after disease onset, indicating that it may be an effective treatment option."

The accumulation of tau "tangles" in Alzheimer's patients has been well documented, though there is no scientific consensus on what triggers the disease. Researchers have long debated the roles of tau and amyloid beta in Alzheimer's. No treatment that targets tau has been approved for Alzheimer's, a field that has seen multiple clinical failures in recent years, though there are experimental therapies in the clinic. The team initially found that acetylation of tau is one of the first hallmark signs in postmortem Alzheimer's diseased brain tissue.

When they took this finding into mice they found that in a model of FTD, when tau is acetylated it lessens the ability for neurons to degrade the protein and thus accumulate, leading to atrophy of the frontotemporal lobe and worsened performance when challenged with standardized memory tests.

They pinned it on p300 inhibition that can acetylate tau in Alzheimer's disease, by blocking tau's acetylation the progression of the disease could be blocked.

A clinical trial using salsalate in a similar tau-mediated neurological condition--progressive supranuclear palsy--is currently underway.

- here's the release
- read the research abstract

Sponsored By Metabolon

Five Translational Insights Key to a Successful First-in-Human (FIH) Study – Metabolite-Based Biomarker Discovery and Validation

Translational success rates from pre-clinical animal studies to human clinical trials remain frustratingly low. Learn how metabolomics helps you bridge between the theoretical & practical, between the function & actual activity of your drug molecule to get you closer to the phenotype, sooner.