Gamma brain waves might prevent cognitive effects of chemotherapy

Phase 2Clinical ResultPhase 1
MIT researchers say a noninvasive treatment could stimulate gamma frequency brain waves and potentially help treat chemo brain. In a study of mice, the researchers delivered daily exposure to light and sound with a frequency of 40 hertz. They found that this protected brain cells from chemotherapy-induced damage — also called chemo brain. The treatment also helped to prevent memory loss and the impairment of other cognitive functions. Originally developed as a way to treat Alzheimer’s disease, the team at MIT says this treatment could have more widespread effects capable of helping with a range of neurological disorders. “The treatment can reduce DNA damage, reduce inflammation, and increase the number of oligodendrocytes, which are the cells that produce myelin surrounding the axons,” Li-Huei Tsai, director of MIT’s Picower Institute for Learning and Memory and the Picower Professor in the MIT Department of Brain and Cognitive Sciences, said in a post on the MIT website. “We also found that this treatment improved learning and memory, and enhanced executive function in the animals.” Tsai serves as the senior author of the new study, which appeared in Science Translational Medicine. The paper’s lead author is TaeHyun Kim, an MIT postdoc. The mice studies run by Tsai and her team found that exposure to light flickering at 40 hertz or sounds with a pitch of 40 hertz and stimulate gamma waves in the brain. This produces protective effects, including the prevention of the rotation of amyloid beta plaques. Using light and sound together provides even more significant protection, MIT says. Phase 1 clinical trial results from humans with early-stage Alzheimer’s also found the treatment safe with some neurological and behavioral benefits. In the new study, the MIT team looked into whether the treatment could counteract the cognitive effects of chemotherapy treatment. Research showed that chemotherapy drugs can induce inflammation on the brain and other detrimental effects, like the loss of white matter. They also promote the loss of myelin, MIT says, and many of these effects are seen in Alzheimer’s. “Chemo brain caught our attention because it is extremely common, and there is quite a lot of research on what the brain is like following chemotherapy treatment,” Tsai said. “From our previous work, we know that this gamma sensory stimulation has anti-inflammatory effects, so we decided to use the chemo brain model to test whether sensory gamma stimulation can be beneficial.” The researchers used mice given cisplatin, a chemotherapy drug commonly used to treat testicular, ovarian, and other cancers, over five days. They then took the mice off the drug for five days, then put them on again for five days. One group received chemotherapy only, while another received 40-hertz light and sound therapy every day. After three weeks, mice that received cisplatin but not gamma therapy displayed many expected effects of chemotherapy. That included brain volume shrinkage, DNA damage, demyelination and inflammation. Those mice also had reduced populations of oligodendrocytes, the brain cells responsible for producing myelin. On the other hand, mice that received gamma therapy with cisplatin showed significant reductions in all of these symptoms. Gamma therapy also had beneficial effects on behavior, MIT says. Mice that received this therapy performed “much better” on tests designed to measure memory and executive function. Using single-cell RNA sequencing, the researchers looked at the gene expression changes that occurred in mice that received the gamma treatment. They saw that, in those mice, inflammation-linked genes and genes that trigger cell death were suppressed. This proved especially true in oligodendrocytes. Mice that received gamma treatment with cisplatin still displayed some beneficial effects visible up to four months later. However, they found that the gamma treatment was much less effective when started three months after chemotherapy ended. They also saw that gamma treatment improved signs of chemo brain in mice that received methotrexate, a different chemotherapy drug. This drug often treats breast, lung and other kinds of cancer. Tsai’s lab now plans to test gamma treatment in mouse models of other neurological disease, including Parkinson’s and multiple sclerosis. Cognito Therapeutics, founded by Tsai and MIT Professor Edward Boyden, completed a Phase 2 trial of gamma therapy in Alzheimer’s patients and plans for a Phase 3 trial this year. “My lab’s major focus now, in terms of clinical application, is Alzheimer’s; but hopefully we can test this approach for a few other indications, too,” Tsai said.
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