Alzheimer’s Disease (AD) patients and the people who are closest to them, suffer for years—the patient suffers the gradual loss of self and the friends and loved ones watch as the person they have known and loved fades away. This contrasts with the sharp, searing pain of loss that goes along with a fatal heart attack. In that case, the pain is acute, but it is quickly over. Friends can mourn, but in short order they can get on with their lives. With Alzheimer’s disease, friends and loved ones must live with the incremental loss that happens day after day. It is like a train wreck in slow motion.
Much work has gone into the study of AD, but the root cause has remained elusive, and thus treatments that have tried to slow the progression of the disease have not proven to be effective.
One hallmark of AD is the formation of amyloid-beta plaques in the brains of patients. It has seemed logical to researchers to seek a cure by eliminating these plaques from patients’ brains. Many treatments aimed at eliminating the plaques have been tried. Some succeeded in reducing or eliminating the plaques, but in no case did these treatments halt or even slow the progression of the disease in test subjects. The plaques are apparently a result of the disease rather than a cause.
Recently, an idea for the mechanism of how the brain is damaged by AD points the way to finding a treatment that counters that mechanism. Fisetin, a bioactive flavonoid, has been shown in experiments to enhance learning and memory in model organisms such as mice and fruit flies. Starting with fisetin, researchers at the Salk Institute in California created a derivative named CMS121. In a paper that appeared in Trends in Pharmacological Sciences, researchers coined the term “geroneuroprotectors.” These substances have the effect of countering the degradation of learning and memory that are common with old age. One of the substances classed as a geroneuroprotector is fisetin and another is CMS121.
The same team that identified the category of geroneuroprotectors, in an article appearing in the September 2020 issue of Redox Biology, discussed the mechanism by which CMS121 works. It is a fatty acid synthase inhibitor, protecting the brain against excessive lipid peroxidation. In so doing, it alleviates the loss of cognition that accompanies AD.
The experiments were run on mice that had been genetically modified to come down with a disease analagous to AD in humans. The results were exciting.
At 9 months of age, mice are at a stage of life corresponding to the beginning of old age in humans. At that age, experimental mice were tested for cognition, and then started on a regimen of 34 mg/kg/day of CMS121. The treatment was continued for three months. At the end of the treatment period, cognitive tests were conducted on the experimental animals, along with two control groups of animals. One control group consisted of age-matched mice that had been genetically modified the same way that the experimental animals were modified. The second control group was wild type (WT) mice that had not been genetically modified to acquire AD.
After the three months of treatment, the mice that were treated with CMS121 performed as well as the WT control mice, but the matched AD mice that had not been treated performed significantly worse. This is good news for people who are growing older and who might be in the early stages of AD. A trial of CMS121 with humans that confirms the safety and efficacy of CMS121 could be a life changer for millions of people.
Until CMS121 becomes available, taking fisetin is something that people can do right now. It can be found in a wide variety of fruits and vegetables. Strawberries are a particularly good source at 160 micrograms of fisetin per gram of strawberry. I don’t need any extra encouragement to eat strawberries. I would eat them even if they didn’t have any therapeutic value.
BIO:
Allen G. Taylor is a 40-year veteran of the computer industry and the author of over 40 books, including Develop Microsoft HoloLens Apps Now, Get Fit with Apple Watch, Cruise for Free, SQL For Dummies, 9th Edition, Crystal Reports 2008 For Dummies, Database Development For Dummies, Access Power Programming with VBA, and SQL All-In-One For Dummies, Third Edition. He lectures internationally on astronomy, databases, innovation, and entrepreneurship. He also teaches database development and Crystal Reports through a leading online education provider. For the latest news on Allen’s activities, check out his blog at wwwallengtaylor.com or contact him at allen.taylor@ieee.org.