Targeted Biomedical Treatment for Autism Spectrum Disorders

Author(s): Iliyana Pacheva*, Ivan Ivanov.

Journal Name: Current Pharmaceutical Design

Volume 25 , Issue 41 , 2019

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Abstract:

Background: A diagnosis of autism spectrum disorders (ASD) represents presentations with impairment in communication and behaviour that vary considerably in their clinical manifestations and etiology as well as in their likely pathophysiology. A growing body of data indicates that the deleterious effect of oxidative stress, mitochondrial dysfunction, immune dysregulation and neuroinflammation, as well as their interconnections are important aspects of the pathophysiology of ASD. Glutathione deficiency decreases the mitochondrial protection against oxidants and tumor necrosis factor (TNF)-α; immune dysregulation and inflammation inhibit mitochondrial function through TNF-α; autoantibodies against the folate receptors underpin cerebral folate deficiency, resulting in disturbed methylation, and mitochondrial dysfunction. Such pathophysiological processes can arise from environmental and epigenetic factors as well as their combined interactions, such as environmental toxicant exposures in individuals with (epi)genetically impaired detoxification. The emerging evidence on biochemical alterations in ASD is forming the basis for treatments aimed to target its biological underpinnings, which is of some importance, given the uncertain and slow effects of the various educational interventions most commonly used.

Methods: Literature-based review of the biomedical treatment options for ASD that are derived from established pathophysiological processes.

Results: Most proposed biomedical treatments show significant clinical utility only in ASD subgroups, with specified pre-treatment biomarkers that are ameliorated by the specified treatment. For example, folinic acid supplementation has positive effects in ASD patients with identified folate receptor autoantibodies, whilst the clinical utility of methylcobalamine is apparent in ASD patients with impaired methylation capacity. Mitochondrial modulating cofactors should be considered when mitochondrial dysfunction is evident, although further research is required to identify the most appropriate single or combined treatment. Multivitamins/multiminerals formulas, as well as biotin, seem appropriate following the identification of metabolic abnormalities, with doses tapered to individual requirements. A promising area, requiring further investigations, is the utilization of antipurinergic therapies, such as low dose suramin.

Conclusion: The assessment and identification of relevant physiological alterations and targeted intervention are more likely to produce positive treatment outcomes. As such, current evidence indicates the utility of an approach based on personalized and evidence-based medicine, rather than treatment targeted to all that may not always be beneficial (primum non nocere).

Keywords: Autism spectrum disorders, mitochondria, pathophysiological mechanisms, biomedical treatment, biomarkers, personalized medicine.

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VOLUME: 25
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Year: 2019
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DOI: 10.2174/1381612825666191205091312
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