Could An Old Arthritis Drug Treat Dementia?

Tau protein shown in red. Credit: Wikimedia commons

In a surprising development, a prescription drug for rheumatoid arthritis may be able to reverse some symptoms of dementia. 

There is great disagreement about what causes Alzheimer's disease. Amyloid beta is the most well known culprit, but another camp believes a protein called Tau is really to blame. Whether one is more important than the other, they both appear to play a role in forming fibrils and plaques. Large amounts of resources have been directed at removing amyloid plaques, but one research team has discovered an old arthritis drug, Salsalate, could remove the tangles caused by Tau. 

Re-purposing an existing drug

The prescription drug Salsalate inhibits a process called tau acetylation by interfering with an enzyme called p300. This is a specific modification in which chemical acetyl group is attached to the tau protein - turning it into a toxic molecule. Scientists believe this acetylated tau is a significant driver of dementia. 

Scientists from the Gladstone Institute discovered that in mice salsalate could lower levels of toxic tau, rescue memory, and even protect the hippocampus from atrophying further - a region particularly effected by dementia. The drug could have beneficial effects in both Alzheimer's patients and fronto-temporal dementia. 

“We identified for the first time a pharmacological approach that reverses all aspects of tau toxicity. 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 Tau protein has not undergone as comprehensive research as its amyloid cousin, so there is no existing drug that targets its build up. After a post-mortem of Alzheimer's patients, researchers noted that tau acetylation is one of the earliest signs of dementia. The toxic form of tau drives a number of negative processes and neurons fail to combat the onslaught, so many believe it's time to target tau as well as amyloid.  

“Targeting tau acetylation could be a new therapeutic strategy against human tauopathies, like Alzheimer’s disease and FTD. Given that salsalate is a prescription drug with a long-history of a reasonable safety profile, we believe it can have immediate clinical implications.”

Because this is a pre-existing drug, there's hope trials could be comparatively speedy. If salsalate proves to have similar effects on human patients, then it could be an excellent way of fighting dementia progression and even help reverse memory loss. 

Read more at Neuroscience News