Arthritis drug 'may help treat Alzheimer's disease'

An "old" drug used to treat rheumatoid arthritis may offer new hope in the fight against Alzheimer's and other forms of dementia, say scientists.

In laboratory mice the anti-inflammatory drug, salsalate, prevented damage to the brain associated with the diseases and reversed memory loss.

The early research points towards an as-yet untried treatment strategy that could be effective in combating the devastating effects of Alzheimer's, it is claimed.

One of the hallmarks of dementia is the formation of so-called tau tangles, toxic twisted knots of protein within nerve cells.

Salsalate was found to inhibit a chemical process called tau acetylation that appears to drive tangle generation.

The drug was tested on genetically engineered mice with frontotemporial dementia (FTD), a form of dementia affecting the frontal lobes of the brain. Tau tangles are a feature of both this disease and Alzheimer's.

Dr Li Gan, from the Gladstone Institute of Neurological Disease in San Francisco, US, who co-led the research, said: "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."

Treatment with the drug protected against shrinkage of the hippocampus, a region of the brain vital to memory, the scientists reported in the journal Nature Medicine.

In maze tests in which mice had to find the location of an escape hole, salsalate restored lost spatial memory, thereby reversing a key symptom of the disease.

The drug worked by blocking an enzyme in the brain called p300 which is known to be raised in Alzheimer's patients and triggers tau acetylation.

Since the enzyme plays an important role in many biological functions, completely inhibiting it could cause serious side effects, the researchers point out.

But they add that according to a recent study p300 activity is "aberrantly high" in Alzheimer's brains.

"Partial inhibition of p300 could normalise its aberrant activation and suppress hyper-acetylation of its substrates, including tau," said the scientists.

Co-author Dr Eric Verdin, from the Gladstone Institute of Virology and Immunology in San Francisco, said: "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."

An estimated 850,000 people in the UK have dementia, and of these at least 60% are suffering from Alzheimer's.

FTD is a much less common disease than Alzheimer's and may account for only around 5% of all cases of dementia.

Dr Simon Ridley, chief scientist at Alzheimer's Research UK, said: "The tau protein is implicated in a number of dementias including Alzheimer's disease and frontotemporal dementia and is a promising target for the development of new treatments.

"This study identifies an important pathway regulating the tau protein in mice which will now need following up in people to explore its potential as a new treatment approach."

Dr Doug Brown, research director at the Alzheimer's Society, said: "None of the current dementia treatments target this specific protein, tau, which creates tangles in the brain that gradually destroy healthy nerve cells. While scientists are still not absolutely sure what causes Alzheimer's or frontotemporal dementia, the hope is that this type of treatment could be one way of slowing down the progression of the disease.

"As this drug is already prescribed to people with arthritis we know a lot about how it works and its side effects - what we need now is confirmation of whether it works for people with dementia.

"Repurposing existing treatments for other conditions offers real hope of delivering a new dementia treatment within five to 10 years."

The charity is funding a number of studies in this area, he added.