Metabolism-Based Treatments for Autism Spectrum Disorder and Co-Morbidities - Abstract
Autism spectrum disorder (hereafter referred to as “ASD”) has broad and heterogeneous clinical manifestations and has been associated with a plethora of possible etiological factors. As such, it has been a challenge to investigate underlying neurobiological mechanisms and to develop effective treatments. Recent studies have increasingly implicated mitochondrial dysfunction as a cause of ASD. Mitochondria are integrally involved in many cellular functions and hence susceptible to many pathophysiological insults. This could explain in part how a wide range of genetic and environmental factors can lead to the consistent behavioural phenotype observed in autistic individuals. Derangements in mitochondrial structure and function – while not unique to diseases such as ASD – nevertheless provide a scientific rationale for experimental therapeutics. Meanwhile, the ketogenic diet (KD), used for nearly a century to treat medically intractable epilepsy, has been shown to enhance mitochondrial function through a multiplicity of mechanisms. This review provides the clinical and basic laboratory evidence for the use of metabolism-based therapies such as the KD in the treatment of ASD, as well as emerging co-morbid models of epilepsy and autism. Future research directions aimed at validating such therapeutic approaches and identifying novel mechanistic targets are also discussed.