Two drugs found that prevent brain cells from dying

The drugs restored memory in mice with FTD and prevented signs of brain cell damage in most mice with prion disease.

Scientists have found two new drugs that can block the pathway leading to the death of brain cells and prevent neuro-degeneration, Medical Xpress reported.

The study, published in the Brain Journal, comes as a follow up to an earlier research in mice where the team from the Medical Research Council [MRC] Toxicology Unit in Leicester had discovered that the accumulated misfold proteins in mice with prion disease over-activate a natural defence mechanism and switch off production of a protein that is vital to brain cells. In several neuro-degenrative diseases, the build-up of misfolded proteins is a major factor in diseases such as Alzheimer’s, Parkinson’s and prion. The researchers tried switching on of the protein production with an experimental drug but found it to be toxic to the pancreas and unsuitable for humans.



For the new study, scientists tested 1,040 compound from the National Institute for Neurological Disorders and Stroke – first in worms as their functioning nervous system is a suitable experimental model, before applying it in mammals.  They found compounds that could be further tested in mouse models of prion disease and a form of familial tauopathy (frontotemporal dementia – FTD).

Led by Professor Giovanna Mallucci, the researchers then identified two drugs that had the ability to restore protein production in mice – trazodone hydrochloride (an anti-depressant) and dibernzoylmethane (a trial compound for anti-cancer drug). The experiments showed that the drugs restored memory in mice with FTD and prevented signs of brain cell damage in most of the mice with prion disease. The drugs also reduced brain shrinkage in both mouse models. For humans, the drugs are already licensed to be used, making the study to be clinical-trial ready.



"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 types of dementia. We could know in two or three years whether this approach can slow down disease progression, which would be a very exciting first step in treating these disorders,” said Mallucci who is now based at the University of Cambridge.

Mallucci, who is also one of the five associate directors of the UK Dementia Research Institute, said: “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."

Apart from the grant by the MRC, the research was also funded by the Alzheimer's Society and Alzheimer's Drug Discovery Foundation.

"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,”  said the director of Research and Development at the Alzheimer’s Society, Dr Doug Brown.



The chief science officer at the MRC, Dr Rob Buckle said: “The study builds on previous work by this team and is a great example of how really innovative discovery science can quite quickly translate into the possibility of real drugs to treat disease."

Speaking to BBC News, Mallucci said it was time for “clinical trials to see if there are similar effects in people and put our money where our mouth is".

"We're very unlikely to cure them completely, but if you arrest the progression you change Alzheimer's disease into something completely different so it becomes liveable with," she added.

Even though the drugs are certified, Mallucci advised that people should “wait for the results”.