Current Enlightenment About Etiology and Pharmacological Treatment of Autism Spectrum Disorder.

Nermin Eissa,Adel Sadeq,Bassem Sadek,Astrid Sasse,Mohammed Al-Houqani,Shreesh K Ojha

doi:10.3389/fnins.2018.00304

Abstract

Autistic Spectrum Disorder (ASD) is a complex neurodevelopmental brain disorder characterized by two core behavioral symptoms, namely impairments in social communication and restricted/repetitive behavior. The molecular mechanisms underlying ASD are not well understood. Recent genetic as well as non-genetic animal models contributed significantly in understanding the pathophysiology of ASD, as they establish autism-like behavior in mice and rats. Among the genetic causes, several chromosomal mutations including duplications or deletions could be possible causative factors of ASD. In addition, the biochemical basis suggests that several brain neurotransmitters, e.g., dopamine (DA), serotonin (5-HT), gamma-amino butyric acid (GABA), acetylcholine (ACh), glutamate (Glu) and histamine (HA) participate in the onset and progression of ASD. Despite of convincible understanding, risperidone and aripiprazole are the only two drugs available clinically for improving behavioral symptoms of ASD following approval by Food and Drug Administration (FDA). Till date, up to our knowledge there is no other drug approved for clinical usage specifically for ASD symptoms. However, many novel drug candidates and classes of compounds are underway for ASD at different phases of preclinical and clinical drug development. In this review, the diversity of numerous aetiological factors and the alterations in variety of neurotransmitter generation, release and function linked to ASD are discussed with focus on drugs currently used to manage neuropsychiatric symptoms related to ASD. The review also highlights the clinical development of drugs with emphasis on their pharmacological targets aiming at improving core symptoms in ASD.

Highlights

Autistic spectrum disorder (ASD) is a biologically based neurodevelopmental disorder affecting two major core behavioral symptoms, namely impairments in social skills and restricted /repetitive behavioral pattern or interest of ASD patients (Baronio et al, 2015)
In addition to numerous reports stating the duplication of 15q11-13 locus in ASD populations, a majority of the cases do not show mutations at this locus. They do exhibit abnormalities in the expression of protein encoded by 15q11-13 gene, as reported. These results demonstrated the involvement of 15q11-13 locus in ASD, either directly by mutation or indirectly by epigenetic factors
Preclinical experimental rodent models are supportive to determine the mechanistic pathways associated with the genetic and environmental targeted insults to the CNS and the pathogenesis of ASD. In recent times these animal models are continuing to proliferate to assess the potential of different drugs and other related treatment modalities. This is of valuable significance, as it may close a gap in our understanding of the effects of therapy and may suggest new and effective methods for ASD treatment

Summary

Introduction

Autistic spectrum disorder (ASD) is a biologically based neurodevelopmental disorder affecting two major core behavioral symptoms, namely impairments in social skills and restricted /repetitive behavioral pattern or interest of ASD patients (Baronio et al, 2015). The clinical application of rivastigmine in ASD children significantly relieved overall ASD behaviors, several adverse effects including nausea, diarrhea, hyperactivity and irritability were reported (Hardan and Handen, 2002; Niederhofer et al, 2002; Nicolson et al, 2006).

Results

Conclusion