Li-Huei Tsai, Director, The Picower Institute for Learning and Memory Picower Professor of Neuroscience, Department of Brain and Cognitive Sciences Senior Associate Member, Broad Institute, at her lab at MIT in Cambridge, MA on 11/23/16. © Bryce Vickmark. All rights reserved. 617.448.6758
Professor Li-Huei Tsai, the project leader

Flashing lights could become a new non-drug treatment for Alzheimer’s disease, according to research at Massachusetts Institute of Technology. Flickering at a particular frequency induces brain waves that help clear toxic proteins.

Experimenting with mice genetically programmed to develop Alzheimer’s, the MIT neuroscientists found that lights flashing on and off 40 times per second restored “gamma oscillation” waves that were suppressed in the disease.

Light treatment for an hour a day over the course of a week led to a marked reduction in brain levels of the toxic amyloid and tau proteins associated with Alzheimer’s. The study is published in the journal Nature.

The researchers have set up a company, Cognito Therapeutics, to commercialise the work. It is discussing a planned clinical trial with the US Food and Drug Administration.

“If humans behave similarly to mice in response to this treatment I would say the potential is just enormous because it is so non-invasive and so accessible,” said Li-Huei Tsai, the project leader. But, she conceded, “it’s a big ‘if’ because so many things have been shown to work in mice, only to fail in humans”.

In any case, she added, demonstrating the underlying importance of particular brain waves had “opened new doors to our understanding of Alzheimer’s”.

As candidate Alzheimer’s drugs — most recently Eli Lilly’s Solanezumab — continue to fail in clinical trials, the MIT research offers a non-pharmaceutical approach “very fundamentally different from all previous attempts”, said Professor Tsai.

“Our non-invasive sensory stimulation does not involve delivering chemicals or antibodies into the body,” she added. “We don’t have to worry about the blood-brain barrier or off-target effects. We directly recruit neurons and other cell types to enable the brain’s inherent ability to repair itself.”

The researchers first used an invasive technique called optogenetics that uses optical fibres to shine light directly on to certain neurons within the mouse’s head. They found that 40 hertz (cycles per second) was the critical frequency required to set up gamma waves in the brain, which cleared deposits of toxic proteins associated with Alzheimer’s.

They then had the idea of doing a non-invasive experiment, simply exposing the animals to 40 hertz flashes from a strip of LEDs in their cages. Treating the mice for an hour a day over the course of a week produced marked reductions in both amyloid and tau proteins.

The therapeutic frequency is about four times faster than strobes in discos but the light does not need to be very bright.

As they design human trials, the researchers are investigating whether the therapy affects the behaviour of Alzheimer’s mice as well as cleaning up the brain — and how it works.

What seems to happen is that gamma waves in the brain, induced by the flashing light, have a healing effect on cells called microglia that are inflamed and unhealthy in Alzheimer’s patients. The microglia play an important role in clearing toxins from the brain.

Alzheimer’s specialists not involved in the study welcomed its findings while emphasising the need for human trials. “While there are no immediate implications for people who are living with dementia, the study might well give us a spark for new avenues of research to further explore the relationship between rhythms of electrical activity in the brain and Alzheimer’s disease,” said Doug Brown, research director of the Alzheimer’s Society.

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