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Two Drugs Being Tested To Prevent Cell Death in Dementia Patients

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Dementia

The pathology of several neurodegenerative diseases, including Alzheimer’s, Parkinson’s and prion diseases, shows an accumulation of misfolded proteins which are thought to contribute to neuronal cell death.

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April 21, 2017 | by Sarah Hand, M.Sc.

Medical Research Council (MRC) scientists have repurposed two drugs to prevent neurodegeneration characteristic of dementia in mouse models. These same researchers – who published their findings in the journal, Brain – originally identified the brain cell death pathway a few years ago.

The pathology of several neurodegenerative diseases, including Alzheimer’s, Parkinson’s and prion diseases, shows an accumulation of misfolded proteins which are thought to contribute to neuronal cell death. Previous work conducted by the MRC researchers found that accumulation of misfolded proteins was associated with inhibition of protein production in the brain cells of mice with prion disease.

While the researchers were able to reverse this process using an experimental drug to allow the neurons to resume regular protein production, the compound proved toxic to the pancreas making it unsuitable for use in human patients. In their current study, the researchers screened over 1,000 compounds and identified two drugs that showed the same neuroprotective effect in mice.

One of the promising compounds identified was trazodone hydrochloride, an antidepressant drug, while the other was dibenzoylmethane (DBM), which is being tested as a possible anti-cancer compound. The drugs were able to reduce brain shrinkage in the mice, as well as prevent signs of brain damage. Mice with frontotemporal dementia also showed restored memory after being treated with the drugs.



“We know that trazodone is safe to use in humans, so a clinical trial is now possible to test whether the protective effects of the drug we see on brain cells in mice with neurodegeneration also applies to people in the early stages of Alzheimer’s disease and other dementias,” said Dr. Giovanna Mallucci, who led the team from the MRC’s Toxicology Unit in Leicester and the University of Cambridge. “We could know in two to three years whether this approach can slow down disease progression, which would be a very exciting first step in treating these disorders.”

This is the first time that a neurodegenerative disease has been effectively stopped in any animal, making it a tremendous step toward one day being able to treat these conditions. For now, it’s unclear whether these drugs would need to be given to patients when they are first diagnosed with Alzheimer’s, and if patients with more advanced forms of dementia would be able to benefit from their use.

“Interestingly, trazodone has been used to treat the symptoms of patients in later stages of dementia, so we know it is safe for this group,” said Mallucci. “We now need to find out whether giving the drug to patients at an early stage could help arrest or slow down the disease through its effects on this pathway.”

According to the Alzheimer’s Association, there are currently over 5 million Americans living with the disease – a number which could grow to 16 million by the year 2050. While drugs like cholinesterase inhibitors can help lessen the symptoms of Alzheimer’s, there is currently no approved treatment which stops the progress of the disease.

“We’re excited by the potential of these findings,” said Dr. Doug Brown, director of research and development at the Alzheimer's Society. “This research is at a very early stage and has not yet been tested in people – but as one of the drugs is already available as a treatment for depression, the time taken to get from the lab to the pharmacy could be dramatically reduced.”


Keywords:  Dementia, Alzheimer's Disease, Drug Discovery


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