Abstract
Autism spectrum disorder (ASD) is a complex, life-long neurodevelopmental disorder currently affecting an estimated 1 out of 68 among children aged 8 y in the United States. ASD has complex genetic and epigenetic features that lead to the phenotype and there is no single genetic marker for the diagnosis. Therefore, the diagnosis for ASD is phenotype- based with no validated or credible laboratory tests available. Evidence-based treatments for ASD are limited. There is no FDA approved medical therapy that addresses either core ASD symptoms or pathophysiological processes associated with ASD. We outline herein, several ASD-associated basic physiological pathways that can be regulated by the small molecule phytochemical sulforaphane, as an example of a druggable small molecule target for which much in vitro, pre-clinical, and clinical evidence already exists: (1) redox metabolism/oxidative stress, (2) mitochondrial dysfunction, (3) immune dysregulation/neuroinflammation, (4) febrile illness and the heat shock response, and (5) synaptic dysfunction. Furthermore, we identify the biomarkers that can be used to assess the functioning of these pathways as well as suggesting how these biomarkers could guide novel treatment strategies to correct these biochemical abnormalities in order to improve core and associated symptoms of ASD.
Keywords: Heat shock response, mitochondrial dysfunction, neuroinflammation, oxidative stress, sulforaphane, synaptic dysfunction.
CNS & Neurological Disorders - Drug Targets
Title:Biomarker-Guided Strategy for Treatment of Autism Spectrum Disorder (ASD)
Volume: 15 Issue: 5
Author(s): Hua Liu, Paul Talalay and Jed W. Fahey
Affiliation:
Keywords: Heat shock response, mitochondrial dysfunction, neuroinflammation, oxidative stress, sulforaphane, synaptic dysfunction.
Abstract: Autism spectrum disorder (ASD) is a complex, life-long neurodevelopmental disorder currently affecting an estimated 1 out of 68 among children aged 8 y in the United States. ASD has complex genetic and epigenetic features that lead to the phenotype and there is no single genetic marker for the diagnosis. Therefore, the diagnosis for ASD is phenotype- based with no validated or credible laboratory tests available. Evidence-based treatments for ASD are limited. There is no FDA approved medical therapy that addresses either core ASD symptoms or pathophysiological processes associated with ASD. We outline herein, several ASD-associated basic physiological pathways that can be regulated by the small molecule phytochemical sulforaphane, as an example of a druggable small molecule target for which much in vitro, pre-clinical, and clinical evidence already exists: (1) redox metabolism/oxidative stress, (2) mitochondrial dysfunction, (3) immune dysregulation/neuroinflammation, (4) febrile illness and the heat shock response, and (5) synaptic dysfunction. Furthermore, we identify the biomarkers that can be used to assess the functioning of these pathways as well as suggesting how these biomarkers could guide novel treatment strategies to correct these biochemical abnormalities in order to improve core and associated symptoms of ASD.
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Cite this article as:
Liu Hua, Talalay Paul and W. Fahey Jed, Biomarker-Guided Strategy for Treatment of Autism Spectrum Disorder (ASD), CNS & Neurological Disorders - Drug Targets 2016; 15 (5) . https://dx.doi.org/10.2174/1871527315666160413120414
DOI https://dx.doi.org/10.2174/1871527315666160413120414 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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