Scientists are delving into the phenomenon where fever seems to temporarily alleviate autism symptoms.
Scientists are delving into the phenomenon where fever seems to temporarily alleviate autism symptoms. Their goal is to understand the underlying cellular and molecular mechanisms, with hopes of developing therapies that replicate this “fever effect” without inducing an actual fever.
Investigating the Fever Effect
Many caregivers have reported that fever can improve autism-related symptoms. This observation is now being rigorously investigated by scientists at MIT and Harvard Medical School, supported by new grants from The Marcus Foundation totaling $2.1 million over three years. The research team aims to uncover the biological processes behind this phenomenon and develop new therapies for autism spectrum disorders (ASD).
“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,” said neuroscientist Gloria Choi, associate professor at The Picower Institute for Learning and Memory and the Department of Brain and Cognitive Sciences at MIT.
The Role of IL-17a
Choi collaborates with Jun Huh, an associate professor of immunology at Harvard Medical School. Their research has shown that the immune molecule IL-17a is crucial in mediating the fever effect in animal studies. The team’s earlier work demonstrated that maternal infection during pregnancy, which alters the mother’s microbiome, can lead to increased levels of IL-17a. This, in turn, affects brain development in the fetus, resulting in autism-like symptoms.
Their studies have revealed that IL-17a can calm hyperactive brain circuits in mice, leading to improved sociability and reduced repetitive behaviors. Notably, even when IL-17a is directly administered to the brains of mice without prior maternal infection, similar improvements in autism-like symptoms were observed.
A Decade of Research
For over ten years, Choi and Huh have explored the links between infection, immune response, and autism. They found that mice exposed to maternal infection during gestation showed autism-like symptoms, which improved when the mice experienced an infection and subsequent fever later in life. This discovery prompted further investigation into how IL-17a and other immune molecules influence brain function and behavior.
In 2020, Choi and Huh’s work clarified that the fever effect in mice with autism-like symptoms depended on the overexpression of IL-17a. This molecule appeared to modulate brain circuits to produce behavioral improvements, offering a potential pathway for therapeutic development.
Future Research and Biobank Initiative
Choi and Huh’s ongoing research seeks to unravel how IL-17a leads to symptom relief and behavior changes. Their project aims to detail the sequence of molecular, cellular, and neural circuit effects triggered by IL-17a and related molecules. This understanding could pave the way for therapies that mimic the fever effect.
To study this effect in humans, Choi and Huh plan to create a biobank of samples from individuals with autism, both those who experience symptom improvements with fever and those who do not, as well as comparable samples from individuals without autism. They will analyze immune system molecules and cellular responses in blood plasma and stool to identify biological markers associated with the fever effect.
Translating Findings into Therapy
If distinct immune response features are identified in those who benefit from the fever effect, this knowledge could inform the development of therapies that replicate these benefits without inducing fever. Understanding how the immune response impacts the brain will be crucial in crafting effective treatments.
“We are enormously grateful and excited to have this opportunity,” said Huh. “We hope our work will ‘kick up some dust’ and make the first step toward discovering the underlying causes of fever responses. Perhaps, one day in the future, novel therapies inspired by our work will help transform the lives of many families and their children with ASD.”
By investigating the immune system’s role in autism and the fever effect, researchers aim to unlock new avenues for treatment, potentially offering significant improvements in the quality of life for those affected by autism spectrum disorders.