Arthritis drug could treat Alzheimer's disease

A drug used to treat rheumatoid arthritis has been found to reverse the symptoms of dementia, according to research published in the journal ‘Nature Medicine’.

Scientists from the Gladstone Institutes in California discovered that anti-inflammatory drug, Salsalate, prevented a toxic protein from building up in the brains of mice and stopped the memory hub from shrinking.

Director of research and development at Alzheimer’s Society, Dr Doug Brown, 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 (FTD).

“None of the current dementia treatments target this specific protein, known as ‘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.”

Researchers suggest that the tau protein accumulates in the brains of people with both Alzheimer’s disease and FTD, which currently effects 850,000 people in the UK.

The study found that Salsalate successfully reversed neurodegeneration and cognitive deficits in a mouse model of FTD. The drug lowered tau levels in the brain, rescued memory impairments, and protected against atrophy of the hippocampus—a brain region essential for memory formation that is impacted by dementia.

Scientists revealed that Salsalate can inhibit the enzyme p300 in the brain, which is elevated in Alzheimer’s disease and triggers acetylation - a chemical process that can change the function and properties of a protein. Blocking tau acetylation can enhance tau turnover and effectively reduce tau levels in the brain. This can reverse the tau-induced memory deficits and prevent loss of brain cells.

Dr Brown continued: “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 ten 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.”

Commenting on the possible use of Salsalate as a treatment for Alzheimer’s disease, Li Gan, an associate investigator at the Gladstone Institutes, added: “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.

“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.”