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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.

U.S. veterans of the wars in Afghanistan and Iraq who suffered mild traumatic brain injury from exposure to explosive blasts were found to have changes in cerebrospinal fluid proteins that are typically seen in people who develop Alzheimer's disease, according to researchers. U.S. veterans of the wars in Afghanistan and Iraq who suffered mild traumatic brain injury from exposure to explosive blasts were found to have changes in cerebrospinal fluid proteins that are typically seen in people who develop Alzheimer's disease, according to researchers at the University of Washington School of Medicine and VA Puget Sound Health Care System. "While our research does not prove that veterans who experienced these injuries will develop Alzheimer's disease, it raises the possibility that they may be on a pathway leading to dementia," said Dr. Ge Li, the paper's first author and an associate professor of psychiatry and behavioral sciences at UW Medicine. The study was published March 13 in the journal Neurology. Previous research has found that sustaining a moderate to severe TBI increases a person's risk of developing Alzheimer's disease. It is not known, however, whether a mild TBI (mTBI) similarly increases this risk. In the new study, the researchers analyzed protein levels in spinal fluid from 51 U.S. veterans of the wars in Afghanistan and Iraq. Each had suffered mTBIs from exposure to explosive blasts and had an average of 20 blast injuries. Those protein levels were compared with the protein levels of 85 veterans and civilians of similar age who had never sustained a TBI. In this study, the veterans were considered to have experienced a TBI if they had an alteration or loss of consciousness from the blast. The TBIs were considered mild if the loss of consciousness lasted 30 minutes or less and there was no sign of brain damage on standard clinical MRI or CT scan. Such an injury is considered equivalent to a concussion. The researchers examined protein levels in the veterans' cerebrospinal fluid, which flows around and through the brain and carries away waste materials. Two of the proteins measured compose the chief components of amyloid plaques, which aggregate in the brains of people with Alzheimer's. These proteins are called alpha-beta amyloid 40 and 42 (Aβ40, Aβ42). The other proteins are versions of the tau protein. Normally, tau proteins are part of cells' cytoskeletons, which give cells their shape. But with Alzheimer's, these structures are changed, creating tangles within brain cells and killing them. This is the other hallmark of Alzheimer's. With Alzheimer's disease, the levels of alpha-beta amyloid proteins in spinal fluid typically decrease. Researchers hypothesize that the proteins, instead of being flushed out into the spinal fluid and carried away as they normally would be, are deposited in amyloid plaques and remain in the brain. As the disease progresses, tau levels, in contrast, tend to be higher than normal, as the proteins are released from dying brain cells. In the study, mTBI veterans in their late 40s and 50s had lower levels of beta-amyloid proteins, compared with the veterans and civilians who had not had such injuries. Tau protein levels also were abnormal in the older mTBI veterans. Normally, tau levels rise as we age. But among the older middle-aged mTBI veterans, levels tended to remain the same, a finding that the normal brain clearance system may not be working as well in among the people with mTBI. Among older mTBI veterans, having lower beta-amyloid 42 levels was also associated with doing less well on cognitive tests assessing verbal memory and fluency. The decline in beta-amyloid proteins, in particular beta-amyloid 42, was concerning, said senior author Dr. Elaine Peskind, a UW research professor of psychiatry and director of the VA's Northwest Mental Illness Research, Education, and Clinical Center. "A decline in beta-amyloid 42 is the earliest detectable change due to Alzheimer's that can be found in a cognitively normal person," she said. "The change can appear as much as 20 years before symptoms. So a person can have the pathology of Alzheimer's going on in their brain but still not have any symptoms -- no problem with their memory or thinking functions -- for as long as 20 years." Peskind and her collaborators suspect the cause of the changes in the mTBI veterans' spinal fluid proteins is due to blast-related damage to a system in the brain, called the glymphatic system, that allows fluids to flow through the brain and carry away waste products. To find out, they have been funded by the National Institute of Neurological Diseases and Stroke to study the regulation and function of this system in veterans with these injuries.

CAMBRIDGE, Mass. & SINGAPORE--(BUSINESS WIRE)-- Sunbird Bio, a biotechnology company developing proprietary protein- and blood-based technologies to improve diagnosis and treatment of neurological disorders and early-stage cancer, today announced that new findings from a study evaluating the correlation between heightened levels of extracellular vesicle (EV)-bound tau in blood and the presence of tau tangles in the brain will be presented at the upcoming Tau2024 Global Conference taking place March 25-26, 2024 in Washington, D.C. “The tau protein is an increasingly important biomarker in the diagnosis and treatment of Alzheimer’s disease and other neurological disorders,” said John McDonough, executive chair and CEO of Sunbird Bio. “Utilizing our APEX diagnostic platform, we are continuing to expand our portfolio of blood-based tests in neurological disorders such as Alzheimer’s disease and Parkinson’s disease. As part of this endeavor, it is important for us to understand the association between EV-bound tau in the blood and the presence of tau tangles in the brain.” The accumulation of tau tangles is a hallmark pathology of Alzheimer's disease, particularly in the later stages of the disease. Many pharmaceutical companies are developing therapeutics that specifically target this protein, but accessible and accurate detection methods are urgently needed. APEX, Sunbird Bio’s lead technology platform, is the first platform that directly detects EV-bound disease-specific proteins that aggregate in the brain. Data to date have shown it is capable of detecting another key Alzheimer’s disease protein, amyloid beta, and other proteins associated with neurological disorders. Following are details about the poster presentation at Tau2024: Topic: The correlation between EV-bound tau proteins in blood and presence of tau tangles in the brain Presenter: Nicholas Ho, Ph.D., Head of Innovation and Scientific Co-Founder, Sunbird Bio Date and Time: Tuesday, March 26, 2024, 10:00AM ET – 10:45AM ET About Sunbird Bio Sunbird Bio is a biotechnology company developing proprietary protein- and blood-based diagnostic tests that provide unprecedented insights to enable earlier, more accurate diagnosis and treatment of neurological disorders and early-stage cancer. Sunbird’s innovative technologies uniquely detect the property and activity of proteins to empower researchers and clinicians with actionable information that is not available or accessible from current tests. Sunbird Bio’s unparalleled leadership in protein- and blood-based diagnostics positions the company to become a global leader in the field, addressing significant research and clinical gaps, and serving multiple, sizable markets. For more information, please visit sunbirdbio.com.