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UC San Diego Team Unveils Three-Hit Metabolic Model for Autism

The paper advances a testable neurometabolic hypothesis, proposing early screening plus antipurinergic trials.

Overview

  • Published on December 9 in Mitochondrion, the study synthesizes more than a decade of systems-biology research into a unified framework.
  • The model posits that autism develops when inherited metabolic sensitivity, an early-life environmental trigger, and prolonged activation of a cell danger response coincide.
  • Chronic dysregulation of extracellular ATP–mediated purinergic signaling is proposed to disrupt mitochondrial function and early brain circuit formation.
  • Authors outline translational steps including prenatal or newborn metabolomic and genetic screening, development of antipurinergic drugs, and larger multi-site clinical trials.
  • Lead author Robert K. Naviaux estimates early identification and metabolic support could prevent or significantly improve about 40–50% of cases, a projection that remains unproven and requires rigorous validation.