The discovery of the first chemical to prevent the death of brain tissue in a neurodegenerative disease has been hailed as the "turning point" in the fight against Alzheimer's disease. More work is needed to develop a drug that could be taken by patients. But scientists say a resulting medicine could treat Alzheimer's, Parkinson's, Huntington's and other diseases. In tests on mice, the Medical Research Council showed all brain cell death from prion disease could be prevented.
Prof Roger Morris, from King's College London, said: "This finding, I suspect, will be judged by history as a turning point in the search for medicines to control and prevent Alzheimer's disease." He told the BBC a cure for Alzheimer's was not imminent but: "I'm very excited, it's the first proof in any living animal that you can delay neurodegeneration.
"The world won't change tomorrow, but this is a landmark study."
The research team at the Medical Research Council Toxicology Unit, based at the University of Leicester, focused on the natural defence mechanisms built into brain cells. When a virus hijacks a brain cell it leads to a build-up of viral proteins. Cells respond by shutting down nearly all protein production in order to halt the virus's spread. However, many neurodegenerative diseases involve the production of faulty or "misfolded" proteins. These activate the same defences, but with more severe consequences. The misfolded proteins linger and the brain cells shut down protein production for so long that they eventually starve themselves to death.
This process, repeated in neurons throughout the brain, can destroy movement or memory or even kill, depending on the disease. This process is thought to take place in many forms of neurodegeneration, so safely disrupting it could treat a wide range of diseases. The researchers used a compound which prevented those defence mechanisms kicking in and in turn halted neurodegeneration. The study, published in Science Translational Medicine, showed mice with prion disease developed severe memory and movement problems. They died within 12 weeks. However, those given the compound showed no sign of brain tissue wasting away.
Lead researcher Prof Giovanna Mallucci told the BBC news website: "They were absolutely fine, it was extraordinary. "What's really exciting is a compound has completely prevented neurodegeneration and that's a first. "This isn't the compound you would use in people, but it means we can do it and it's a start." She said the compound offered a "new pathway that may well give protective drugs" and the next step was for drug companies to develop a medicine for use in humans.
Prof Mallucci's lab is also testing the compound on other forms of neurodegeneration in mice but the results have not yet been published. Side effects are an issue. The compound also acted on the pancreas, meaning the mice developed a mild form of diabetes and lost weight. Any human drug would need to act only on the brain. However, this gives scientists and drug companies a starting point.
David Allsop, professor of neuroscience at Lancaster University described the results as "very dramatic and highly encouraging" but cautioned that more research was needed to see how the findings would apply to diseases such as Alzheimer's and Parkinson's.
Dr Eric Karran, the director of research at the charity Alzheimer's Research UK, said: "Targeting a mechanism relevant to a number of neurodegenerative diseases could yield a single drug with wide-reaching benefits, but this compound is still at an early stage.
"It will be important for these findings to be repeated and tested in models of other neurodegenerative diseases, including Alzheimer's disease."
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