Treatment of Autism Spectrum Disorders by Mitochondrial-targeted Drug: Future of Neurological Diseases Therapeutics

Abstract

Abstracts: Autism is a neurodevelopmental disorder with a complex etiology that might involve environmental and genetic variables. Recently, some epidemiological studies conducted in various parts of the world have estimated a significant increase in the prevalence of autism, with 1 in every 59 children having some degree of autism. Since autism has been associated with other clinical abnormalities, there is every possibility that a sub-cellular component may be involved in the progression of autism. The organelle remains a focus based on mitochondria's functionality and metabolic role in cells. Furthermore, the mitochondrial genome is inherited maternally and has its DNA and organelle that remain actively involved during embryonic development; these characteristics have linked mitochondrial dysfunction to autism. Although rapid stride has been made in autism research, there are limited studies that have made particular emphasis on mitochondrial dysfunction and autism. Accumulating evidence from studies conducted at cellular and sub-cellular levels has indicated that mitochondrial dysfunction's role in autism is more than expected. The present review has attempted to describe the risk factors of autism, the role of mitochondria in the progression of the disease, oxidative damage as a trigger point to initiate mitochondrial damage, which manifests as Autism Spectrum Disorders (ASD), genetic determinants of the disease, possible pathogenic pathways and therapeutic regimen in vogue and the developmental stage. Furthermore, in the present review, an attempt has been made to include the novel therapeutic regimens under investigation at different clinical trial stages and their potential possibility to emerge as promising drugs against ASD.

Metabolomic changes in children with autism

“…However, the estimates of the co-occurrence of mitochondrial disorders in individuals with ASD range from 5% to 80%[ 130 ]. Many factors increase the prevalence of mitochondrial dysfunction in children with autism, such as genetic mutations, dietary deficiencies of vitamins and minerals in the diet, certain chemicals and heavy metals exposure, some drugs, certain bacterial and viral infections, and stressful conditions[ 131 ]. Mitochondrial dysfunction can arise from genetic mutations in mitochondrial DNA (mtDNA) or nuclear DNA, affecting the function of mitochondrial proteins and enzymes[ 132 , 133 ].…”

Polyphenols: Natural Food-Grade Biomolecules for the Treatment of Nervous System Diseases from a Multi-Target Perspective

“…Furthermore, cumulative damage and oxidative stress may affect the onset or severity of autism and its comorbidities by reducing the ability to produce functional mitochondria. Increased ROS production brought on by dysfunctional mitochondria may also cause chronic oxidative stress [48,49].…”

Polyphenols: Natural Food-Grade Biomolecules for the Treatment of Nervous System Diseases from a Multi-Target Perspective

“…Furthermore, cumulative damage and oxidative stress may affect the onset or severity of autism and its comorbidities by reducing the ability to produce functional mitochondria. Increased ROS production brought on by dysfunctional mitochondria may also cause chronic oxidative stress [ 95 , 96 ].…”