A Potential Breakthrough

A new therapy developed by researchers at the Jawaharlal Nehru Center for Advanced Scientific Research (JNCASR) offers a promising avenue for individuals with autism spectrum disorder (ASD) or intellectual disability. This novel approach aims to mitigate the debilitating effects of these conditions, perhaps enabling patients to lead more independent lives.

Unlike current treatments that primarily focus on managing symptoms, this therapy targets the underlying mechanisms of these neurodevelopmental disorders. current therapeutics prescribed to treat autism spectrum disorder (ASD) or intellectual disability are mostly related to alleviating the symptoms. These do not correct the phenotypes observed in neurodevelopmental disorders, especially after brain development. This new research seeks to address the core issues, even after notable brain development has occurred.

The Science Behind the Therapy

The research, conducted on mice, centered on a gene that is often repressed in the brains of individuals with autism. The team, led by Tapas K Kundu and James Clement from JNCASR, discovered a crucial link between this gene and the acetylation of DNA-associated proteins.

Specifically,the study focused on mice with a mutated syngap gene,mirroring the genetic makeup of some autistic patients. In mice with mutated syngap gene – which resembles humans with mutated syngap gene (present in autistic patients) – the acetylation of DNA-associated proteins, histones, or proteins that provide structural support for chromosomes is repressed in the brain, the team explained. Thay identified KAT3B, also known as p300, as the epigenetic enzyme responsible for this acetylation.

Building on previous work, Kundu’s group had identified TTK21 as an activator of the KAT3B enzyme. By conjugating this activator with a glucose-derived nanosphere (CSP-TTK21), the researchers developed a method to deliver the activator directly to the brain.

Restoring Brain Function

The results of the study, published in the journal Aging Cell, were encouraging. When CSP-TTK21 was administered to the Syngap1 autistic mice, it successfully induced acetylation in the brain. More importantly, it led to a restoration of neuronal function, improved learning and memory, and facilitated neuronal rearrangements.

Notably,these positive effects were observed even when the treatment was administered after the brain was considered to be developed,equivalent to adolescence in humans. this suggests that the therapy could potentially benefit older individuals with autism or intellectual disability.

This report not only directly connects histone acetylation with autism, for the first time, but also opens a very optimistic door for ASD therapy.
JNCASR Researchers

A New Therapeutic Avenue

The study’s findings offer a new perspective on treating Syngap1-related intellectual disability and ASD. By targeting epigenetic modifications, the therapy aims to restore deficits to a degree that allows patients to achieve greater independence.

The researchers emphasize the potential impact of this approach: The study provides a new potential therapeutic option by targeting epigenetic modifications in Syngap1-related intellectual disability /ASD that can restore the deficits to an extent that will enable the patient to lead a life less dependent on others.