A painkiller widely used to treat rheumatoid arthritis has been shown to reverse the symptoms of dementia in the brains of laboratory mice, raising hope that there may soon be an effective treatment for Alzheimer’s disease, scientists have said.
The drug, salsalate, is a licensed pain killer but in mice with a form of dementia similar to Alzheimer’s it reversed the changes to a key protein in the brain that builds up in patients with the debilitating neurological disease, they found.
The researchers said it is the first time any drug has been shown to have an effect on the “tau” protein that accumulates in the brain of people with Alzheimer’s and a range of similar dementias known as “tauopathies”. It could lead to an effective therapy even for patients in the later stages of disease, the researchers said.
“We identified for the first time a pharmacological approach that reverses all aspects of tau toxicity," said Li Gan, PhD of the Gladstone Institutes, a non-profit research organisation affiliated with the University of California, San Francisco.
“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,” said Dr Gan a senior co-author of the study published in the journal Nature Medicine.
As many as 800,000 people in Britain are already affected by Alzheimer’s disease and a new study has suggested that as many as one in three babies born this year will get dementia in their lifetime, largely as a result of people living longer. Age is the biggest risk factor for the disease.
People in the late stages of the disease suffer from a build of the tau protein, which forms that damaging “neurofibrillary tangles” that are a primary marker of Alzheimer’s disease. Tau has long been a target for drug development, but with little success.
The study involved laboratory mice suffering from another form of dementia, called frontotemporal dementia (FTD), which also involves the acetylation of the tau protein. (AFP/Getty)
The latest study, however, found that salsalate is able to reverse the chemical changes to the tau protein that are involved in the formation of the neurofibrillary tangles that gradually poison the brain, causing memory loss and other symptoms of dementia.
Dr Gan and her colleagues found that tau proteins undergo a chemical change called acetylation which acts as a driver for the accumulation of tau proteins and the associated toxicity. They believed that preventing or reversing the acetylation may have an impact on the brain degeneration of the tauopathies - including Alzheimer’s.
They found that salsalate inhibits an enzyme in the brain known as p300, which is higher than normal in patient with Alzheimer’s and appears to trigger acetylation of the tau protein.
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The study involved laboratory mice suffering from another form of dementia, called frontotemporal dementia (FTD), which also involves the acetylation of the tau protein. The scientists showed that by blocking the p300 enzyme using salsalate, the mice recovered their memory ability as well as having reduced levels of the damaging tau protein in their brains.
“Targeting tau acetylation could be a new therapeutic strategy against human tauopathies, like Alzheimer's disease and FTD," said Eric Verdin, a senior investigator at the Gladstone Institutes and co-author of the study published in the journal Nature Medicine.
“Given that salsalate is a prescription drug with a long-history of a reasonable safety profile, we believe it can have immediate clinical implications,” Dr Verdin said.
Doug Brown, director of research and development at Alzheimer’s Society, said: “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. Salsalate is currently in a clinical trial for another brain disease, progressive supranuclear palsy, and we look forward to seeing the results as they could be indicative of its potential as a treatment for dementia.
“Repurposing existing treatments for other conditions offers real hope of delivering a new dementia treatment within five to 10 years – which is why Alzheimer’s Society is currently funding a number of studies in this area, including a treatment for type 2 diabetes and another drug for arthritis.”
