In a groundbreaking study, Indian scientists have uncovered a potential therapy that may significantly reduce dependency in individuals with Autism Spectrum Disorder (ASD) and Intellectual Disability (ID), offering a ray of hope for families and caregivers worldwide.
Led by Prof. Tapas K. Kundu and Dr. James Clement at the Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Bengaluru—an autonomous institute under India’s Department of Science and Technology—the research team has discovered a way to restore brain function in a mouse model of autism by modulating epigenetic markers in the brain.
Unlocking the Autism Epigenetic Code
The study focuses on SYNGAP1, a gene known to play a critical role in brain development and synaptic function. Mutations in this gene are strongly associated with ASD and ID, impairing learning, memory, and social behavior. While previous efforts in autism therapeutics have largely targeted behavioral symptoms, this new approach goes a step further—addressing underlying biological mechanisms even after the brain has developed.
The researchers found that Syngap1+/- mice—genetically modified to mimic human autism symptoms—display repressed acetylation of histone proteins in the brain. This repression was linked to the reduced activity of the p300/CBP acetyltransferase enzymes, which are responsible for modifying the structure of DNA to enable gene expression critical for brain function.
To counter this, the team used a molecule called TTK21, previously discovered by Kundu’s group as an activator of p300. They then combined TTK21 with a glucose-derived carbon nanosphere (CSP) to create CSP-TTK21, allowing for targeted delivery into the brain.
Reversing the Autism Phenotype
When administered to adolescent Syngap1+/- mice, CSP-TTK21 successfully restored histone acetylation levels, improved neurogenesis, boosted synaptic function, and even normalized behavioral patterns—bringing them close to their wild-type counterparts.
Published in the prestigious journal Aging Cell, the study is being hailed as a landmark in autism research. For the first time, it establishes a direct link between histone acetylation and autism, demonstrating the potential to reverse autistic traits by correcting epigenetic modifications.
What This Means for Patients
Most autism therapies today focus on behavioral interventions or symptom management. This study suggests a biological route that could help restore lost functions and promote independence in affected individuals—even during adolescence or adulthood, a phase typically considered too late for developmental intervention.
“This opens up an entirely new therapeutic window for treating neurodevelopmental disorders like autism,” said Prof. Kundu.
“Our work offers the first evidence that altering the epigenetic landscape can reverse behavioral and neurobiological deficits associated with SYNGAP1 mutations.”
A Glimpse into the Future
Beyond ASD, the implications of this study are far-reaching. The ability to modulate gene expression through epigenetic intervention could pave the way for novel treatments in other neurodevelopmental and neurodegenerative conditions.
The research also highlights several key genes—Adcy1, Ntrk3, Egr1, and Foxj1—whose expression was restored through CSP-TTK21 treatment, all known to play vital roles in brain plasticity and development.
A New Therapeutic Horizon
While human trials are still a future step, this preclinical success sets the stage for further exploration into non-invasive, targeted epigenetic therapies for autism. As the field of neuroepigenetics grows, studies like this provide a critical roadmap for developing therapies that not only manage but potentially reverse the impact of neurodevelopmental disorders.
Paper Title: Epigenetic modulation rescues neurodevelopmental deficits in Syngap1+/− mice https://onlinelibrary.wiley.com/action/showCitFormats?doi=10.1111%2Facel.14408
Journal: Aging Cell
Institutions Involved: JNCASR, DST India
Lead Authors: Tapas K. Kundu and James Clement
