‘Repurposed’ drugs can reduce brain shrinkage linked to Alzheimer’s disease

TWO “repurposed” drugs have been shown to reduce the kind of brain shrinkage caused by Alzheimer’s and other neurodegenerative diseases.

Both medicines, one a licensed antidepressant and the other an anti-cancer compound, restored protein production in the brains of laboratory mice.

The drugs blocked an important pathway linked to brain cell death caused by prion disorders such as Creutzfeldt-Jakob disease, and dementia.

Brain damage was prevented in mice with prion disease and animals with frontotemporal dementia (FTD) reclaimed their memory. In both cases, brain shrinkage was reduced.

The antidepressant trazodone hydrochloride and anti-cancer drug dibenzoylmethane (DBN) were identified after scientists tested 1,040 compounds on laboratory worms and mammalian cells.

Professor Giovanna Mallucci, who led the team from the Medical Research Council’s Toxicology Unit in Leicester and Cambridge University, said: “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.

“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.

“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.

“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.”

Dr Doug Brown, director of research and development at the Alzheimer’s Society, said: “We’re excited by the potential of these findings.

“They show that a treatment approach originally discovered in mice with prion disease might also work to prevent the death of brain cells in some forms of dementia.

“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.

“The drug blocks a natural defence mechanism in cells which is overactive in the brains of people with frontotemporal dementia, Alzheimer’s disease and Parkinson’s, so has the potential to work for several conditions.”

The results appear in the journal Brain.

Neuropathologist Dr Payam Rezaie, from the Open University, said: “This is not a cure for neurodegenerative diseases or dementia, it will not reverse the course of illness, and the neuroprotective effects were observed in the majority of, but not in all experimental animals.

“Nevertheless, it could represent a significant step forward in attempting to halt these diseases in their tracks, and as the researchers state, considering its existing licence for use in elderly patients, trazodone in particular would be a potential candidate for clinical trials moving forward.”