Epigenetic Therapy Shows Promise in Restoring Cognitive Function in Autism Model Mice

A study by Tapas K Kundu and James Clement from JNCASR demonstrates potential for improving patient independence and learning capabilities in autism spectrum disorder (ASD). Current treatments primarily alleviate symptoms without addressing the underlying phenotypes, particularly after brain development. The research, conducted on mice, identified a gene repressed in the brains of autistic patients. The team stated that "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 epigenetic enzyme responsible for this acetylation is identified as KAT3B or p300. Kundu's group previously discovered TTK21, an activator of this enzyme. Conjugating this activator with a glucose-derived nanosphere (CSP-TTK21) and administering it to Syngap1 autistic mice induced acetylation in the brain. The research, published in *Aging Cell*, revealed that CSP-TTK21 restored neuronal function, learning, and memory, and induced neuronal rearrangements in Syngap1 mice. This was observed primarily when administered after brain development, equivalent to adolescence in humans. Researchers state that "This report not only directly connects histone acetylation with autism, for the first time, but also opens a very optimistic door for ASD therapy." The study suggests a new therapeutic approach by targeting epigenetic modifications in Syngap1-related intellectual disability/ASD, potentially restoring deficits to improve patient independence.