Summary: Researchers are studying how fever can temporarily improve autism symptoms. They aim to understand the cellular and molecular mechanisms at the origin of this “fever effect” in order to develop therapies that imitate it.
Their research focuses on the immune molecule IL-17a, which has shown promise in animal studies. By creating a biobank of samples from individuals with and without autism, the team hopes to translate these findings into effective treatments.
Highlights:
- Fever effect: Fever may temporarily improve autism symptoms, prompting research aimed at mimicking this effect.
- Immune concentration: The immune molecule IL-17a is a key factor in this improvement, as shown in animal studies.
- New therapies: Researchers aim to develop treatments based on the fever effect without causing an actual fever.
Source: MIT
Scientists are catching up with what parents and other caregivers have been reporting for many years: When some people with autism spectrum disorder have an infection that triggers a fever, their autism-related symptoms appear to improve.
Thanks to two new grants from the Marcus Foundation, scientists from MIT and Harvard Medical School hope to explain how this happens with the goal of eventually developing therapies that mimic the “fever effect” to similarly improve symptoms.
“Although not actually triggered by fever per se, ‘the fever effect’ is real and it provides us with an opportunity to develop therapies to alleviate the symptoms of autism spectrum disorders,” said the neuroscientist Gloria Choi, associate professor at The Picower Institute for Learning and Memory and the Department of Brain and Cognitive Sciences at MIT.
Choi will collaborate on the project with Jun Huh, associate professor of immunology at Harvard Medical School. Together, the grants awarded to the two institutions provide $2.1 million over three years.
“To the best of my knowledge, ‘the fever effect’ is perhaps the only natural phenomenon in which developmentally determined symptoms of autism improve significantly, albeit temporarily,” Huh said.
“Our goal is to learn how and why this happens at the cellular and molecular level, identify immunological factors, and produce persistent effects that benefit a broad group of people with autism.” »
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.
“I have long been interested in new approaches to treating and alleviating the symptoms of autism, and Drs. Choi and Huh have refined a bold theory,” said Bernie Marcus, founder and president of the Marcus Foundation.
“I hope this Marcus Foundation Medical Research Award will help their theory come to fruition and ultimately help improve the lives of children with autism and their families.” »
Brain-immunity interaction
For a decade, Huh and Choi have been studying the link between the infection and autism. Their studies suggest that the beneficial effects associated with fever may come from molecular changes in the immune system during infection, rather than the rise in body temperature per se.
Their work in mice showed that maternal infection during pregnancy, modulated by the composition of the mother’s microbiome, can lead to neurodevelopmental abnormalities in offspring that lead to autism-like symptoms, such as impaired sociability.
Huh and Choi’s labs traced the effect at high maternal levels of a type of immune signaling molecule called IL-17a, which acts on receptors on brain cells in the developing fetus, leading to hyperactivity in a region of the cerebral cortex called S1DZ.
In another study, they showed how maternal infection appears to prompt offspring to produce more IL-17a upon infection later in life.
Building on these studies, a 2020 article clarified the effect of fever in the context of autism. This research showed that mice that developed symptoms of autism following maternal infection while in utero would show improvements in their sociability when they had infections – a finding that mirrored observations in people.
The scientists found that this effect depended on the overexpression of IL-17a, which in this context appeared to calm affected brain circuits.
When scientists delivered IL-17a directly to the brains of mice with autism-like symptoms whose mothers had not been infected during pregnancy, the treatment still produced improvement in symptoms.
New studies and samples
This work suggests that mimicking the “fever effect” by administering supplemental IL-17a could produce similar therapeutic effects for multiple autism spectrum disorders, with different underlying causes.
But the research also left wide open questions that will need to be answered before a clinically viable therapy can be developed. How exactly does IL-17a cause symptom relief and behavioral change in mice? Does the fever effect work the same way in humans?
In the new project, Choi and Huh hope to answer these questions in detail.
“By learning the science behind the effect of fever and knowing the mechanism behind the improvement of symptoms, we can have enough knowledge to be able to imitate it, even in individuals who do not naturally feel the effect of the fever. fever,” Choi said.
Choi and Huh will continue their work in mice, seeking to uncover the sequence of effects on molecular, cellular, and neuronal circuits triggered by IL-17a and similar molecules that lead to enhanced sociability and a reduction in repetitive behaviors. .
They will also delve deeper into why immune cells from mice exposed to maternal infection are primed to produce IL-17a.
To study the effect of fever in humans, Choi and Huh plan to establish a “biobank” of samples from autistic volunteers who may or may not have symptoms associated with fever, as well as comparable non-autistic volunteers.
Scientists will measure, catalog and compare these immune system molecules and cellular responses in blood plasma and stool to determine biological and clinical markers of fever effect.
If research reveals distinct cellular and molecular features of the immune response in people with improved fever, researchers could harness this knowledge into a therapy that mimics the benefits of fever without causing an actual fever.
Detailing how the immune response works in the brain would help determine how therapy should be designed to produce similar effects.
“We are extremely grateful and excited to have this opportunity,” Huh said. “We hope that our work will “kick up some dust” and take the first step toward uncovering the underlying causes of febrile reactions. Perhaps one day in the future, new therapies inspired by our work will help transform the lives of many families and their children with ASD.
About this autism research news
Author: David Orenstein
Source: MIT
Contact: David Orenstein – MIT
Picture: Image is credited to Neuroscience News
News Source : neurosciencenews.com
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