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Credit: https://www.mercurynews.com/2017/01/04/diagnosing-alzheimers-medicare-now-pays-doctors-to-stop-and-assess-memory-loss/

Alzheimer’s-like memory decline is reversible

August 18, 2020

Scientists at the Salk Institute have successfully reversed memory loss in mouse models using a new molecule
The group used a drug called CMS121 that changes how cells metabolize lipids
Their experiments showed that mice who with Alzheimer’s-equivalent disease do as well as healthy controls after treatment with CMS121
The researchers are excited about identifying a new target for Alzheimer’s-like memory decline and are pursuing clinical trials

Salk Institute researchers say a drug that has been previously found to slow aging in brain cells can successfully reverse memory decline in mice with inherited Alzheimer’s-equivalent disease. The findings were published in the scientific journal Redox Biology. The new molecule, CMS121, changes how brain cells metabolize lipids (fat cells). “This was a more rigorous test of how well this compound would work in a therapeutic setting than our previous studies on it,” says Pamela Maher, senior staff scientist in the lab of Salk Professor David Schubert and the senior author of the new paper. “Based on the success of this study, we’re now beginning to pursue clinical trials.” For several decades now, scientists have been studying a molecule called fisetin which is present in vegetables and fruits. Researchers have found fisetin can improve memory and slow down brain cell degeneration. The Salk team synthesized different variants of fisetin and found that the one called CMS121 was particularly effective at preventing Alzheimer’s-like symptoms in mouse models. Maher and colleagues tested CMS121 in mice with the equivalent of inherited Alzheimer’s. The team gave one subset of 9-month-old (middle-aged) mice daily doses of CMS121. At this age, mice already begin to show decline in memory and learning. The doses of CMS121 were timed to mimic human patients who visit doctors for cognitive problems. At 12 months old, after receiving 3 months of CMS121 treatment, the mice were subjected to various behavior and memory tests. In both types of testing, the mice with Alzheimer’s-like disease who received CMS121 performed as well as healthy controls. The untreated mice, on the other hand, performed poorly in comparison. The team wanted to better understand how CMS121 impacts memory, behavior, and learning. They compared lipid levels between the three groups of mice (healthy, treated, and untreated). The researchers found that untreated mice with Alzheimer’s-like disease have several differences in comparison to healthy mice and mice treated with CMS121. Specifically, a process called lipid peroxidation was identified. Lipid peroxidation is a breakdown of lipids (fat cells) and leads to the production of free radicals that can cause cell damage. The mice with Alzheimer’s-like disease who did not receive CMS121 had higher levels of lipid peroxidation compared to the mice treated with CMS121. “That not only confirmed that lipid peroxidation is altered in Alzheimer’s, but that this drug is actually normalizing those changes,” says Salk postdoctoral fellow Gamze Ates, first author of the new paper. The scientists further showed that CMS121 lowers lipid peroxidation by lowering the levels of a protein called FASN (fatty acid synthetase). Upon analysis of human brain samples of patients who had died of Alzheimer’s, the researchers found these patients had higher levels of FASN than people of similar age with healthy cognition. These findings suggest that FASN could be a target for Alzheimer’s treatments. The Salk Institute team is pursuing clinical trials and hope that other scientists will explore FASN and lipid peroxidation as targets for Alzheimer’s. “There has been a big struggle in the field right now to find targets to go after,” says Maher. “So, identifying a new target in an unbiased way like this is really exciting and opens lots of doors.”

References: https://www.sciencedaily.com/releases/2020/08/200804165119.htm?utm_source=feedburner&utm_medium=email&utm_campaign=Feed%3A+sciencedaily%2Fhealth_medicine%2Fhealthy_aging+%28Healthy+Aging+News+--+ScienceDaily%29%22%20target=%22_blank%22%20rel=%22noopener%22%3Ehttps://www.sciencedaily.com/releases/2020/08/200804165119.htm?utm_source=feedburner&utm_medium=email&utm_campaign=Feed%3A+sciencedaily%2Fhealth_medicine%2Fhealthy_aging+%28Healthy+Aging+News+--+ScienceDaily%29%22%20target=%22

Alzheimer’s-like memory decline is reversible

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