Alzheimer's disease has been reversed in mice with a drug that mimics the benefits of exercise to the brain. The revolutionary therapy generated new neurons, improving the lab animals' thinking skills by destroying rogue proteins that cause the devastating illness. It raises the possibility of developing medications that fuel the production of brain cells known as neurogenesis. Senior author Professor Rudolph Tanzi, director of the Genetics and Ageing Research Unit at Massachusetts General Hospital, said: 'In our study we showed exercise is one of the best ways to turn on neurogenesis. The revolutionary therapy at Massachusetts General Hospital generated new neurons, improving the lab animals' thinking skills by destroying rogue proteins that cause the devastating illness. The authors say they strongly believe it will be true for humans, too 'Then, by figuring out the molecular and genetic events involved, we determined how to mimic the beneficial effects of exercise through gene therapy and pharmacological agents.' The US team say they hope a similar technique may work in humans. Plans to explore this are already underway. Lead author Dr Se Hoon Choi, based at the same lab, said: 'While we do not yet have the means for safely achieving the same effects in patients, we determined the precise protein and gene targets for developing ways to do so in the future.' Even one 30 minute brisk walk, jog or bike ride pumps extra blood to the brain, delivering the oxygen and nutrients it needs to perform to its best. This improves mental functions by promoting the birth of neural progenitor cells in the hippocampus, the area of the brain that controls memory. Experiments in adult mice genetically engineered to develop Alzheimer's like symptoms showed these new neurons could be induced either by exercise or drugs and gene therapy. At first only exercise worked. This is because physical activity turns on a protein called BDNF which is known to protect brain cells. Dr Choi explained: 'We found the key difference was that exercise also turned on the production of brain-derived neurotrophic factor or BDNF - known to be important for the growth and survival of neurons - which created a more hospitable brain environment for the new neurons to survive. 'By combining drugs and gene therapy that both induced neurogenesis and increased BDNF production, we were able to successfully mimic the effects of exercise on cognitive function.' In behaviour tests animals in which neurogenesis had been caused by exercise had improved cognitive performance and reduced levels of beta amyloid. These are the rogue proteins that form into clumps in the brains of Alzheimer's patients. The mice in which it had been induced pharmacologically and genetically displayed only limited benefits, until the administration of BDNF. Tanzi said: 'Although exercise-induced AHN improved cognition in Alzheimer's mice by turning on neurogenesis, trying to achieve that result by using gene therapy and drugs did not help. 'That was because newly born neurons, induced by drugs and gene therapy, were not able to survive in brain regions already ravaged by Alzheimer's pathology, particularly neuroinflammation. So we asked how neurogenesis induced by exercise differs.' The study published in Science shows those benefits can be blocked by inflammation in the brain of patients with Alzheimer's. Physical activity can 'clean up' the environment, allowing new nerve cells to survive and thrive and improving cognition in the Alzheimer's mice. Tanzi added: 'The lesson learned was it is not enough just to turn on the birth of new nerve cells, you must simultaneously 'clean up' the neighbourhood in which they are being born to make sure the new cells survive and thrive. 'Exercise can achieve that, but we found ways of mimicking those beneficial cognitive effects by the application of drugs and gene therapy that simultaneously turn on neurogenesis and BDNF production.' The researchers also found blocking neurogenesis in younger mice with Alzheimer's shortly after birth led to more pronounced cognitive deficits later in life. Tanzi said: 'We will next explore whether safely promoting neurogenesis in Alzheimer's patients will help alleviate the symptoms of the disease and whether doing so in currently healthy individuals earlier in life can help prevent symptoms later on. 'We are very excited to now investigate ways of implementing our new findings to more effectively treat and prevent this terrible disease.'
A study conducted by researchers at Massachusetts General Hospital has shown that Alzheimer’s disease can be reversed in mice by drugs and gene therapy that mimic the benefits of exercise to the brain. The therapy turns on neurogenesis and facilitates destruction of rogue proteins called beta amyloids, thus improving the mice’s cognitive skills. In a new study, published online today in Nature Neuroscience, scientists from Harvard Medical School show how they used this approach to reverse memory loss associated with Parkinson’s disease.