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Content archived on 2023-03-24

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Gene injection promises a new weapon in the fight against Alzheimer’s

Research funded jointly by the European Research Council (ERC) and Alzheimer’s Research UK has demonstrated that the crippling neurodegenerative disease could be stopped by an injection into the memory centres of the brain.

Published in the journal ‘Proceedings of the National Academy of Sciences’, the research team based at Imperial College London have shown that it’s possible to deliver a gene which produces a plaque-busting protein directly into the brain. The degeneration of brain cells in Alzheimer’s disease is largely due to amyloid plaques. The sticky protein build-up happens when amyloid proteins fold and divide improperly. The main component of these protein clumps are amyloid-beta peptides. Preventing these proteins from forming may help prevent the death of brain cells which causes the disease and its symptoms to escalate. Nearly 9 million people in Europe suffer from Alzheimer’s. The research team studied a gene called PGC-1a as previous research had suggested that the gene could prevent the formation of amyloid plaques. They injected the gene into mice that were in the early stages of Alzheimer’s disease. The mice did not develop any plaques and performed as well in memory tasks as healthy mice after four months. Dr Magdalena Sastre, senior author of the research, commented that these findings could eventually provide a method of preventing the disease or halting it in the early stages. ‘Although these findings are very early, they suggest this gene therapy may have potential therapeutic use for patients. There are many hurdles to overcome, and at the moment the only way to deliver the gene is via an injection directly into the brain,’ she expanded. ‘However, this proof of concept study shows this approach warrants further investigation.’ To administer the gene, the team used a harmless lentivirus that was modified to include the gene. The virus then infects brain cells and rewrites their genetic code to produce more of the plaque-fighting PGC-1a. Injections were administered in the hippocampus and cortex of the brain, as these are responsible for memory formation and orientation, and are the first to be affected by Alzheimer’s disease. Professor Nicholas Mazarakis, co-author of the study and recipient of the ERC’s IRLVGTMND project grant, added: ‘Scientists harness the way the lentivirus infects cells to produce a modified version of the virus that delivers genes into specific cells. It is being used in experiments to treat a range of conditions from arthritis to cancer. We have previously successfully used the lentivirus vector in clinical trials to deliver genes into the brains of Parkinson’s disease patients.’ Dr Doug Brown, Director of Research and Development of the UK’s Alzheimer’s Society also commented: ‘So far potential treatments that directly target amyloid build-ups in the brain have mostly had disappointing results in clinical trials, whereas this study could pave the way for a new plan of attack.’ The team’s results suggest that therapies utilising PGC-1a may be able to prevent Alzheimer’s disease if the patient is treated early. Human trials are still a long way off but this provides new hope for the development of a treatment for a currently incurable disease. For more information, please see: project page on CORDIS

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