Understanding why autism symptoms sometimes improve amid fever

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Understanding why autism symptoms sometimes improve amid fever

Understanding why autism symptoms sometimes improve amid fever

With support from The Marcus Foundation, an MIT neuroscientist and a Harvard Medical School immunologist will study the “fever effect” in an effort to devise therapies that mimic its beneficial effects.

David Orenstein<br>The Picower Institute for Learning and Memory

Publication Date:

May 23, 2024

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David

Orenstein

Email:<br>davidjo@mit.edu

Phone:<br>617-324-2079

Picower Institute

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When some people with autism spectrum disorders experience an infection (the most outward sign is a fever), some of their autism symptoms improve during that time. A new research project aims to understand why that happens so that it might be mimicked to produce a therapy.

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Scientists are catching up to what parents and other caregivers have been reporting for many years: When some people with autism spectrum disorders experience an infection that sparks a fever, their autism-related symptoms seem to improve.<br>With a pair of new grants from The Marcus Foundation, scientists at MIT and Harvard Medical School hope to explain how this happens in an effort to eventually develop therapies that mimic the “fever effect” to similarly improve symptoms.<br>“Although it isn’t actually triggered by the fever, per se, the ‘fever effect’ is real, and it provides us with an opportunity to develop therapies to mitigate symptoms of autism spectrum disorders,” says neuroscientist Gloria Choi, associate professor in the MIT Department of Brain and Cognitive Sciences and affiliate of The Picower Institute for Learning and Memory.<br>Choi will collaborate on the project with Jun Huh, associate professor of immunology at Harvard Medical School. Together the grants to the two institutions provide $2.1 million over three years.<br>“To the best of my knowledge, the ‘fever effect’ is perhaps the only natural phenomenon in which developmentally determined autism symptoms improve significantly, albeit temporarily,” Huh says. “Our goal is to learn how and why this happens at the levels of cells and molecules, to identify immunological drivers, and produce persistent effects that benefit a broad group of individuals with autism.”<br>The Marcus Foundation has been involved in autism work for over 30 years, helping to develop the field and addressing everything from awareness to treatment to new diagnostic devices.<br>“I have long been interested in novel approaches to treating and lessening autism symptoms, and doctors Choi and Huh have honed in on a bold theory,” says Bernie Marcus, founder and chair of The Marcus Foundation. “It is my hope that this Marcus Foundation Medical Research Award helps their theory come to fruition and ultimately helps improve the lives of children with autism and their families.”<br>Brain-immune interplay<br>For a decade, Huh and Choi have been investigating the connection between infection and autism. Their studies suggest that the beneficial effects associated with fever may arise from molecular changes in the immune system during infection, rather than on the elevation of body temperature, per se.<br>Their work in mice has shown that maternal infection during pregnancy, modulated by the composition of the mother’s microbiome, can lead to neurodevelopmental abnormalities in the offspring that result in autism-like symptoms, such as impaired sociability. Huh’s and Choi’s labs have traced the effect to elevated maternal levels of a type of immune-signaling molecule called IL-17a, which acts on receptors in brain cells of the developing fetus, leading to hyperactivity in a region of the brain’s cortex called S1DZ. In another study, they’ve shown how maternal infection appears to prime offspring to produce more IL-17a during infection later in...

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