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Scientists pave way for simple pill to cure Alzheimer's

MELANIE FOSTER

SCIENTISTS have hailed a historic "turning point" in the search for a medicine that could beat Alzheimer's disease, after a drug-like compound was used to halt brain cell death in mice for the first time.

Although the prospect of a pill for Alzheimer's remains a long way off, the landmark British study provides a major new pathway for future drug treatments.

The compound works by blocking a faulty signal in brains affected by neurodegenerative diseases. The signal shuts down the production of essential proteins, leading to brain cells being unprotected and dying off.

The compound was tested in mice with prion disease - the best animal equivalent of human neurodegenerative disorders - and human clinical trials could take between five and 10 years. But scientists said they were confident the same principles would apply in humans with debilitating brain diseases such as Alzheimer's or Parkinson's.

The study, published today in the journal Science Translational Medicine, was carried out at the Medical Research Council's (MRC) Toxicology Unit at the University of Leicester.

"It's a real step forward," team leader Professor Giovanna Mallucci said.

"It's the first time a substance has been given to mice that prevents brain disease. The fact that this is a compound that can be given orally, that gets into the brain and prevents brain disease, is a first in itself… We can go forward and develop better molecules and I can't see why preventing this process should only be restricted to mice. I think this probably will translate into other mammalian brains."

In debilitating brain diseases like Alzheimer's, the production of new proteins in the brain is shut down by a build-up of "misfolded proteins" or amyloids. This build-up leads to an "over-activation" of a natural defence mechanism that stops essential proteins being produced. Without these proteins to protect them, brain cells die off - leading to the symptoms of diseases like Alzheimer's.

The compound used in the study works by inhibiting an enzyme, known as PERK, which plays a key role in activating this defence mechanism. In mice with prion disease, it restored proteins to protect brain cells "stopping the disease in its tracks", restoring some normal behaviours and preventing memory loss.

Although the compound also produced significant side-effects in mice - including weight loss and mild diabetes - Professor Mallucci said it would "not be impossible" to develop a drug that protected the brain without the side-effects and that work towards doing so had been "very promising".

The breakthrough was greeted with excitement by scientists, who said that while it is not a guarantee of an Alzheimer's cure in the near future, it remains a significant proof of principle.

Professor Roger Morris, acting head of King's College London's department of chemistry, believed the finding "will be judged by history as a turning point in the search for medicines to control and prevent Alzheimer's disease".

"This is the first convincing report that a small drug, of the type most conveniently turned into medicines, stops the progressive death of neurons in the brain as found, for instance, in Alzheimer's disease," he said.

"True, this study has been done in mice, not man; and it is prion disease, not Alzheimer's, that has been cured.

However, there is considerable evidence that the way neurons die in both diseases is similar; and lessons learned in mice from prion disease have proved accurate guides to attenuate the progress of Alzheimer's disease in patients.

"From finding the first effective drug in a mouse, to having an effective medicine in man usually takes decades to bring to fruition… So, a cure for Alzheimer's is not just around the corner. However, the critical point of principle made by… [the] study is that a drug… can arrest neurodegeneration caused by amyloid in the brain."

David Allsopp, professor of neuroscience at Lancaster University, said the study had thrown up "very dramatic and highly encouraging results", but said that more research was needed to overcome the "problematic side-effects" and to prove the technique would be effective against other diseases like Alzheimer's and Parkinson's.

There are currently 800,000 people in the UK with dementia and Alzheimer's disease is the most common cause.

Dr Eric Karran, director of research at Alzheimer's Research UK, said: "What is true in animals does not always hold true in people and the ultimate test for this compound will be to see whether it is safe and effective in people with these diseases."

Topics:  alzheimers, editors picks, medicine, research




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