Noninvasive chemobrain therapy

Gamma entrainment alleviates chemo-induced cognitive decline.

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Chemotherapy patients frequently have “chemo brain” or cognitive problems such as memory loss and concentration problems. Researchers at MIT have found that a noninvasive therapy that uses sound and light at a frequency of 40 hertz can shield brain cells from the damaging effects of chemotherapy.

This treatment prevented memory loss and cognitive impairment in mice. Originally designed for Alzheimer’s, it shows promise for various neurological disorders.

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, “The treatment can reduce DNA damage, reduce inflammation, and increase the number of oligodendrocytes, which are the cells that produce myelin surrounding the axons. We also found that this treatment improved learning and memory and enhanced executive function in the animals.”

Years ago, Tsai and her team explored using light flickering at 40 hertz to improve Alzheimer’s cognitive symptoms. Gamma oscillations, important for attention and memory, are frequently compromised in Alzheimer’s patients.

Tsai’s mouse studies showed that 40 hertz of light or sound can stimulate protective gamma waves, preventing amyloid beta plaques. Combining light and sound enhances protection. Phase 1 trials on early Alzheimer’s patients found the treatment safe with some neurological benefits.

The purpose of the trial was to determine whether the treatment could mitigate the cognitive effects of chemotherapy. Chemotherapy can cause brain inflammation and loss of white matter, similar to Alzheimer’s effects. According to Tsai, chemo brain is a typical occurrence, so they investigated whether their sensory gamma stimulation—which has anti-inflammatory properties—could be beneficial.

The researchers used mice given cisplatin, a chemotherapy drug, as their experimental model. Mice were given cisplatin for five days, off for five, and then back on for five. One group received only chemotherapy, whereas the other received sound and light treatment every day at 40 Hz. After three weeks, the mice in the chemotherapy-only group displayed the anticipated side effects, such as inflammation, DNA damage, and brain atrophy.

They also had fewer oligodendrocytes, which were responsible for myelin. However, mice with gamma therapy had fewer symptoms and better memory and function.

Researchers looked at alterations in gene expression in mice after gamma therapy using single-cell RNA sequencing. They discovered that genes linked to inflammation and cell death were downregulated, particularly in oligodendrocytes, which are the cells that produce myelin.

Some benefits persisted up to four months after gamma treatment alongside cisplatin, but less so if started three months post-chemo. Gamma treatment also improved chemobrain signs in mice given methotrexate, another chemotherapy drug used for various cancers.

Tsai said, “I think this is a fundamental mechanism to improve myelination and promote the integrity of oligodendrocytes. It seems that it’s not specific to the agent that induces demyelination, be it chemotherapy or another source of demyelination.”

Tsai’s lab is testing gamma therapy in animal models for Parkinson’s disease and multiple sclerosis, among other neurological conditions. Co-founded by Tsai and Professor Edward Boyden of MIT, Cognito Therapeutics just finished a phase 2 trial for patients with Alzheimer’s and is preparing for a phase 3 trial this year.

In conclusion, the noninvasive treatment involving light and sound therapy at 40-hertz shows promise in mitigating the cognitive effects of chemotherapy, commonly referred to as “chemo brain.”

In mice models, this medication has shown considerable improvements in memory and executive function, as well as in lowering inflammation and safeguarding brain cells. More investigation and clinical trials are necessary to confirm its efficacy and investigate its possible use in treating chemobrain and other neurological illnesses in humans.

Journal reference:

  1. Kim, TaeHyun; James, Benjamin T et al., Gamma entrainment using audiovisual stimuli alleviates chemobrain pathology and cognitive impairment induced by chemotherapy in mice. Science Translational Medicine. DOI:10.1126/scitranslmed.adf4601.
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