A major pathway leading to brain cell death in mice has been blocked by an orally administered drug-like compound, successfully preventing neurodegeneration in the animals.

While this particular compound also resulted in unacceptable weight loss, the finding provides a new target for future drugs to treat neurodegenerative disorders in humans, such as Alzheimer’s and Parkinson’s diseases.

The study, published in Science Translational Medicine, found that the compound, originally developed by the pharmaceutical company GlaxoSmithKline for a different purpose, was able to enter the brain from the bloodstream and halt a neurodegenerative disease throughout the whole brain.

The mice had prion disease – from a family of rare progressive neurodegenerative disorders known as transmissible spongiform encephalopathies, of which Creutzfeldt-Jakob disease (CJD) is an example in humans.

Previous work by the researchers, from the Medical Research Council’s (MRC) toxicology unit at the University of Leicester, found that the “build-up of mis-folded proteins in the brains” of mice with prion disease caused the over-activation of a natural defence mechanism in cells, switching off the production of new proteins.

This protein production – key to the survival of brain cells – would normally switch on again, but the build-up of misshapen protein prevented this and led to brain cell death.

That previous discovery, published in the journal Nature in 2012, led to the scientists’ idea that this pathway could be switched off.

Professor Giovanna Mallucci, the MRC scientist who led the team of researchers, says: “Our previous study predicted that this pathway could be a target for treatment to protect brain cells in neurodegenerative disease. So we administered a compound that blocks it to mice with prion disease.”

Prof. Mallucci adds:

We were extremely excited when we saw the treatment stop the disease in its tracks and protect brain cells, restoring some normal behaviours and preventing memory loss in the mice.”

However, the researchers say that despite protecting the brain, the compound also produced weight loss in the mice and mild diabetes due to damage to the pancreas, calling a halt to further investigation in the animals.

“We’re still a long way from a usable drug for humans – this compound had serious side effects,” Prof. Mallucci says. But she remains optimistic:

The fact that we have established that this pathway can be manipulated to protect against brain cell loss – first with genetic tools and now with a compound – means that developing drug treatments targeting this pathway for prion and other neurodegenerative diseases is now a real possibility.”

Prof. Mallucci’s colleague Professor Hugh Perry, chair of the MRC’s neuroscience and mental health board, added his thoughts on the importance of the new research.

“Misshapen proteins in prion diseases and other human neurodegenerative disorders, such as Alzheimer’s and Parkinson’s, also over-activate this fundamental pathway [that controls] protein synthesis in the brains of patients,” Prof. Perry says, who is also professor of experimental neuropathology at the UK’s University of Southampton.

“Despite the toxicity of the compound used, this study indicates that, in mice at least, we now have proof-of-principle of a therapeutic pathway that can be targeted,” Prof. Perry adds.

“This might eventually aid the development of drugs to treat people suffering from dementias and other devastating neurodegenerative diseases.”

Treatment of diseases such as Parkinson’s is not the only challenge – effective diagnosis is, too. There is no biological test for Parkinson’s disease, but research published in the journal Neurology earlier in October 2013 found that a biomarker for the disorder may lie just under the skin.