Alzheimer’s breakthrough: Scientists may have found potential cause of the disease

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Scientists have broken new ground in the search for an Alzheimer's cure, discovering a new potential cause of the disease, which it may be possible to target with drug treatments. Experts said the findings, from Duke University in North Carolina, USA, could "open new doors" in the increasingly frustrated global hunt for a dementia therapy. Researchers at Duke announced that their studies of Alzheimer's in mice had thrown up a new process they believe contributes to the disease's development. They observed that in Alzheimer's, immune cells that normally protect the brain instead begin to consume a vital nutrient called arginine. By blocking this process with a drug, they were able to prevent the formation of 'plaques' in the brain that are characteristic of Alzheimer's disease, and also halted memory loss in the mice. While no technique that is tested in an animal can be guaranteed to work the same way in humans, the findings are particularly encouraging because, until now, the exact role of the immune system and arginine in Alzheimer's was completely unknown The drug that was used to block the body's immune response to arginine — known as difluoromethylornithine (DFMO) — is already being investigated in drug trials for certain types of cancer and may be suitable for testing as a potential Alzheimer's therapy. The discovery was welcomed by experts in the UK who said it had filled in gaps in our understanding of Alzheimer's and could "open new doors" to future treatments for the devastating condition, which affects more than 500,000 people in the UK alone. A new drug target for Alzheimer's would be hugely welcome a field where funding and industry's will to invest has been waning, in spite of the growing human and economic cost of Alzheimer's and other forms of dementia. Costly failures The number of people worldwide living with some form of dementia is set to reach 135 million by 2050. However, after a string of costly failures to bring effective drugs to market, pharmaceutical companies are increasingly cutting funding for research. The G8 group of nations pledged in 2013 to find a major new dementia treatment or cure by 2025, and the Coalition government committed the UK to doubling its contribution toward this goal to $164 million by that date. Carol Colton, professor of neurology at the Duke University, and senior author of the new study, said that Alzheimer's research had been dominated by an attempt to understand the role of amyloid — the protein that builds up in the brain to form plaques — but that a focus on arginine and the immune system could yield new discoveries. "We see this study opening the doors to thinking about Alzheimer's in a completely different way, to break the stalemate of ideas in Alzheimer's disease," she said. "The field has been driven by amyloid for the past 15, 20 years and we have to look at other things because we still do not understand the mechanism of disease or how to develop effective therapeutics," she added. Arginine is an amino acid and an essential nutrient for several bodily processes, including cell division, healing and immune responses. It is found in food, including dairy products, meat, nuts and chickpeas, but the team at Duke said that their study did not suggest eating more arginine would have an impact on Alzheimer's risk. The blood-brain barrier regulates how much arginine can enter the brain, and the immune response that breaks down arginine would remain the same even if confronted with higher levels of the nutrient. Their study, which is published in the Journal of Neuroscience, was led by Matthew Kan, an MD/PhD student in Professor Colton's lab. Dr Laura Phipps, from Alzheimer's Research UK, said that because the research had only been carried out in mice it would be important for tests in humans to confirm the findings. "Clinical trials are essential before any potential new treatment can be given to people, but these early findings could open new doors for future treatment development for Alzheimer's," she said. "The study suggests that low levels of arginine in the brain could contribute to the death of nerve cells in Alzheimer's, but there is much more we still need to understand about how and why nerve cells die in the disease," she added. Dr James Pickett, head of research at the Alzheimer's Society said the new study "joins some of the dots in our incomplete understanding of the processes that cause Alzheimer's disease". "Importantly, these new findings reflect earlier observations that arginine is reduced in the brains of people," he said.  BY CHARLIE COOPER/THE INDEPENDENT