One of the world’s oldest drugs which was first mentioned by Hippocrates in the 5th Century BC could help restore memory in Alzheimer’s patients, scientists hope.
Salsalate, which comes from the same family as aspirin, was typically used to treat inflammatory conditions like rheumatoid arthritis.
But a new study suggests that it can prevent the build-up of toxic proteinsin the brain and even reverse damage already done, unblocking pathways and restoring memory.
Although the effects have only been seen in mice so far, scientists believe trials could quickly move to humans because researchers already know that the drug is safe and produces few side-effects.
The US scientists say it is the first time that a drug has been shown to reverse all toxic effects of the tau protein and Alzheimer’s charities said the discovery was ‘promising news.’
Tau proteins accumulate in people which dementia, driving neurodegeneration and mental decline. But a low dose of salsalate appears to lower tau levels ‘rescuing’ memories and protecting the hippocampus – a part of the brain essential for forming memories.
“We identified for the first time a pharmacological approach that reverses all aspects of tau toxicity,” said Dr Li Gan, an associate investigator at the Gladstone Institutes, University of California.
“We found that salsalate reversed memory loss in a mouse model of dementia. These mice, which exhibit AD-related tau pathology, develop spatial memory loss at 7-months of age. We treated these mice with salsalate for about two months, and their memory loss is reversed.
“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.”
Hippocrates first described salicylates as a bitter powder extract from willow bark that eased aches and pains and reduced fevers.
The active extract salicin was first isolated by the German chemist Johann Andreas Buchner in 1828 and it can exist in two forms salsalate and aspirin.
Salsalate prevented the accumulation of tau by blocking an enzyme.
“Targeting tau could be a new therapeutic strategy against Alzheimer’s disease,” says co author Dr Eric Verdin, a senior investigator at the Gladstone Institutes.
“Given that salsalate is a prescription drug with a long-history of a reasonable safety profile, we believe it can have immediate clinical implications.”
Salsalate, which has largely been replaced by more modern drugs, is also being looked at as a possible treatment for diabetes.
Dr Doug Brown, Director of Research and Development at Alzheimer’s Society, said: “It’s promising news that the arthritis drug salsalate could potentially reduce the accumulation of one of the toxic proteins that characterises both Alzheimer’s disease and Frontotemporal dementia. 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.”
Dr Simon Ridley, Head of Research at Alzheimer’s Research UK, added: “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.
“Understanding more about the biology of the diseases that cause dementia is vital for identifying important biological processes to target with new treatments, and to highlight parallels with other health conditions where treatments may already exist.
“This study explores a drug previously used to treat rheumatoid arthritis, but further research will now need to explore the potential for this treatment to affect levels of the tau protein in people with Alzheimer’s and frontotemporal dementia.
“While there is potential that drugs used to treat other diseases could hold benefit in dementia, nobody should be taking such drugs until clinical trials have shown them to be safe and effective for the treatment of dementia.”
The research was published in the journal Nature Medicine.