Those participating in World Alzheimer’s Day (September 21) got unexpectedly positive news as researchers announced that a widely used arthritis pain killer has reversed the symptoms of dementia in lab mice, welcome results for those dealing with HIV-related dementia. The new study, published in the journal Nature Medicine, discovered that the drug salsalate reversed changes to a key protein that’s similar to the one impacted by Alzheimer’s debilitating dementia.
This is the first time that anymedication has been shown to have this impact on the protein “tau,” which accumulates in the brains of those with Alzheimer’s and a range of similar dementias known as “tauopathies.”
“We identified for the first time a pharmacological approach that reverses all aspects of tau toxicity," Li Gan the paper’s senior author told U.K.’s Independent.
The finding suggests the drug could become the first treatment able to not just slow but actually reverse the effects of the neurological disease, which currently impacts as many as five million Americans. People living with HIV may show signs of dementia or Parkinson's as early as their 50s or 60s.
“Dementia and neuropathy are more common in older patients with HIV,” Dr. Victor Valcour of University of California, San Francisco (UCSF) told researchers at the 2007 Evolving Mechanisms of HIV Neuropathogenesis in the HAART era: Domestic and Global Issues meeting in Venice, Italy. Theo Smart from AIDSMAP reported that Valcour describing data from his own study. HIV-related dementia is associated with memory problems, social withdrawal, and trouble concentrating. While HIV-related dementia is a disorder distinct from Alzheimer’s, as people with HIV are living longer, more are at risk of developing some form of dementia, which is why this new study is so hopeful.
“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 Gan who works for the Gladstone Institutes, a non-profit research organization affiliated with UCSF.
As the tau protein builds up in people’s brains, it forms damaging “neurofibrillary tangles," which are indicators of the Alzheimer’s disease that slowly poison the brain, causing memory loss and other symptoms of dementia.
Reducing the tau buildup has long been a target for drug development, but until now there has been no success. This latest study may change all of that. The scientists used the pain medication to treat laboratory mice suffering from a similar form of dementia, called frontotemporal dementia. In the lab mice, salsalate actually reversed the chemical changes to the tau protein associated in the formation of the neurofibrillary tangles.
Gan and her colleagues found that salsalate blocked a particular enzyme known as p300, and in doing so restored memory ability to the sick mice. In addition, blocking p300 reduced the levels of the damaging tau protein.
“Given that salsalate is a prescription drug with a long-history of a reasonable safety profile, we believe it can have immediate clinical implications,” Eric Verdin, a senior investigator at the Gladstone Institutes and co-author of the study, said in a written statement.
Doug Brown, director of research and development at Britain’s Alzheimer’s Society, agreed, speaking to the Independent, “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.”
Researchers (and pharmaceutical companies) are now interested in the potential of combining or repurposing existing treatment to see if the resulting therapies can be used for other conditions.
Brown added that the Alzheimer’s Society is investing in this new approach. “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.”