A noninvasive treatment may protect patients from memory impairment and cognitive effects of chemotherapy

Sufferers present process chemotherapy usually expertise cognitive results similar to reminiscence impairment and problem concentrating—a situation generally generally known as “chemo mind.”

MIT researchers have now proven {that a} noninvasive therapy that stimulates gamma frequency mind waves might maintain promise for treating chemo brain. In a examine of mice, they discovered that every day publicity to mild and sound with a frequency of 40 hertz protected mind cells from chemotherapy-induced harm. The therapy additionally helped to stop memory loss and impairment of different cognitive features.

This therapy, which was initially developed as a technique to deal with Alzheimer’s illness, seems to have widespread results that might assist with a wide range of neurological problems, the researchers say.

“The therapy can cut back DNA harm, cut back irritation, and enhance the variety of oligodendrocytes, that are the cells that produce myelin surrounding the axons,” says Li-Huei Tsai, director of MIT’s Picower Institute for Studying and Reminiscence and the Picower Professor within the MIT Division of Mind and Cognitive Sciences. “We additionally discovered that this therapy improved studying and reminiscence, and enhanced government operate within the animals.”

Tsai is the senior writer of the brand new examine, which appears in Science Translational Drugs. The paper’s lead writer is TaeHyun Kim, an MIT postdoc.

Protecting mind waves

A number of years in the past, Tsai and her colleagues started exploring using mild flickering at 40 hertz (cycles per second) as a means to enhance the cognitive signs of Alzheimer’s illness. Earlier work had urged that Alzheimer’s sufferers have impaired gamma oscillations—mind waves that vary from 25 to 80 hertz (cycles per second) and are believed to contribute to mind features similar to consideration, notion, and reminiscence.

Tsai’s studies in mice have discovered that publicity to mild flickering at 40 hertz or sounds with a pitch of 40 hertz can stimulate gamma waves within the mind, which has many protecting results, together with stopping the formation of amyloid beta plaques.

Utilizing mild and sound collectively offers much more important safety. The therapy additionally seems promising in people: Section I clinical trials in folks with early-stage Alzheimer’s illness have discovered the therapy is protected and does supply some neurological and behavioral advantages.

Within the new examine, the researchers got down to see whether or not this therapy may additionally counteract the cognitive effects of chemotherapy therapy.

Analysis has proven that these medication can induce irritation within the mind, in addition to different detrimental results similar to lack of white matter—the networks of nerve fibers that assist totally different elements of the mind talk with one another. Chemotherapy medication additionally promote lack of myelin, the protecting fatty coating that permits neurons to propagate electrical alerts. Many of those results are additionally seen within the brains of individuals with Alzheimer’s.

“Chemo mind caught our consideration as a result of this can be very frequent, and there’s various analysis on what the mind is like following chemotherapy therapy,” Tsai says. “From our earlier work, we all know that this gamma sensory stimulation has anti-inflammatory results, so we determined to make use of the chemo mind mannequin to check whether or not sensory gamma stimulation will be useful.”

As an experimental mannequin, the researchers used mice that got cisplatin, a chemotherapy drug usually used to deal with testicular, ovarian, and different cancers. The mice got cisplatin for 5 days, then taken off of it for 5 days, then on once more for 5 days. One group acquired chemotherapy solely, whereas one other group was additionally given 40-hertz mild and sound remedy each day.

After three weeks, mice that acquired cisplatin however not gamma remedy confirmed lots of the anticipated results of chemotherapy: mind quantity shrinkage, DNA harm, demyelination, and irritation. These mice additionally had diminished populations of oligodendrocytes, the mind cells chargeable for producing myelin.

Nonetheless, mice that acquired gamma remedy together with cisplatin therapy confirmed important reductions in all of these signs. The gamma remedy additionally had useful results on conduct: Mice that acquired the remedy carried out significantly better on assessments designed to measure reminiscence and government operate.

‘A basic mechanism’

Utilizing single-cell RNA sequencing, the researchers analyzed the gene expression changes that occurred in mice that acquired the gamma therapy. They discovered that in these mice, inflammation-linked genes and genes that set off cell dying had been suppressed, particularly in oligodendrocytes, the cells chargeable for producing myelin.

In mice that acquired gamma therapy together with cisplatin, among the useful results may nonetheless be seen as much as 4 months later. Nonetheless, the gamma therapy was a lot much less efficient if it was began three months after the chemotherapy ended.

The researchers additionally confirmed that the gamma therapy improved the indicators of chemo mind in mice that acquired a distinct chemotherapy drug, methotrexate, which is used to deal with breast, lung, and different forms of most cancers.

“I believe this can be a very basic mechanism to enhance myelination and to advertise the integrity of oligodendrocytes. Evidently it is not particular to the agent that induces demyelination, be it chemotherapy or one other supply of demyelination,” Tsai says.

Due to its widespread results, Tsai’s lab can also be testing gamma treatment in mouse fashions of different neurological illnesses, together with Parkinson’s illness and a number of sclerosis. Cognito Therapeutics, an organization based by Tsai and MIT Professor Edward Boyden, has completed a Section II trial of gamma remedy in Alzheimer’s sufferers, and plans to start a Section III trial this 12 months.

“My lab’s main focus now, when it comes to scientific software, is Alzheimer’s; however hopefully we will take a look at this method for a number of different indications, too,” Tsai says.

This story is republished courtesy of MIT Information (web.mit.edu/newsoffice/), a well-liked website that covers information about MIT analysis, innovation and instructing.