Critical windows and reversibility of autism associated with mutations in chromatin remodelers

  • Awarded: 2020
  • Award Type: Research
  • Award #: 707964

Neurodevelopmental conditions, such as autism spectrum disorder (ASD) and intellectual disability, affect more than three percent of children worldwide, yet in the majority of cases, therapeutic options and supports are limited. Several cardinal questions need to be answered in order to shorten the gap between genetic discoveries and their translation to the clinic.

For example, we know very little about when during nervous system development ASD mutations exert their effects and which brain structures are critically affected. Similarly, it remains essentially unknown whether ASD core symptoms can be treated after their onset. This culminates in the notion that we have nearly no knowledge of how to design clinical trials with regard to developmental and therapeutic temporal windows. Thus, it will be impossible to develop successful treatment strategies without answering these fundamental questions, even with hypothetical optimal therapeutic targets.

In a previous SFARI Pilot Award, Gaia Novarino studied Setd5 conditional knockout mice during development and adulthood1. In the current project, Novarino plans to study conditional mouse models of other chromatin modifiers that are also ASD risk genes, including ASH1L and KMT5B. She plans to study their roles during development and in adulthood, as well as gain an understanding of the bases of their potential reversibility. Such analyses are critical to developing therapeutic strategies and designing appropriate clinical trials for individuals with ASD associated with mutations in this class of genes.


1.Deliu E. et al Nat. Neurosci. 21, 1717-1727 (2018) PubMed
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