1. A new job for old drugs
Two existing drugs can block cell death in mice.
Building on an earlier breakthrough, Professor Giovanna Mallucci and her team at the University of Cambridge have identified two drugs that can block the death of brain cells in mice with a neurodegenerative disease. The drugs target a natural defence mechanism in cells called the unfolded protein response. This response is activated when 'misfolded' proteins build up in several diseases where brain cells degenerate, including Alzheimer's.
Professor Mallucci said, 'We screened through over 1,000 different compounds in the lab to find ones that could block the unfolded protein response and found two promising drug candidates.'
The drugs, an antidepressant called trazodone and a compound found in liquorice called dibenzoylmethane, were tested in mice that had prion-related diseases. Prions are toxic misfolded proteins that cause Creutzfeldt-Jakob disease. They provide a useful model to study neurodegeneration. The study showed that the drugs protected brain cells from dying.
The researchers also tested the drugs on mice with frontotemporal dementia. They were particularly looking at how drugs affected the protein tau, which forms harmful clumps in several forms of dementia, including Alzheimer's disease. They found that the drugs were also able to prevent the death of brain cells and improve memory abilities in these mice.
Dr Doug Brown, Director of Research and Development at Alzheimer's Society, said, 'We're excited by the potential of these findings. They show that a treatment approach originally discovered while researching prion disease might also work to prevent the death of brain cells in some forms of dementia.'
The next steps are for these drugs to be tested in animals that have Alzheimer's disease and to begin testing the antidepressant - already a licensed drug - in people in the earlier stages of Alzheimer's.
'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 apply to people in the early stages of Alzheimer's disease or other dementias,' says Professor Mallucci.
Despite trazodone being an existing medication, Professor Mallucci advised against jumping to conclusions until further research is completed. Its benefits need to be weighed carefully against potential side effects before it can be approved for people with early stages of dementia.
The findings were published in the journal Brain, and the research was funded by the Medical Research Council, Alzheimer's Society and Alzheimer Drug Discovery Foundation.