Treatments for Biomedical Abnormalities Associated with Autism Spectrum Disorder

Abstract

Recent studies point to the effectiveness of novel treatments that address physiological abnormalities associated with autism spectrum disorder (ASD). This is significant because safe and effective treatments for ASD remain limited. These physiological abnormalities as well as studies addressing treatments of these abnormalities are reviewed in this article. Treatments commonly used to treat mitochondrial disease have been found to improve both core and associated ASD symptoms. Double-blind, placebo-controlled (DBPC) studies have investigated l-carnitine and a multivitamin containing B vitamins, antioxidants, vitamin E, and co-enzyme Q10 while non-blinded studies have investigated ubiquinol. Controlled and uncontrolled studies using folinic acid, a reduced form of folate, have reported marked improvements in core and associated ASD symptoms in some children with ASD and folate related pathway abnormities. Treatments that could address redox metabolism abnormalities include methylcobalamin with and without folinic acid in open-label studies and vitamin C and N-acetyl-l-cysteine in DBPC studies. These studies have reported improved core and associated ASD symptoms with these treatments. Lastly, both open-label and DBPC studies have reported improvements in core and associated ASD symptoms with tetrahydrobiopterin. Overall, these treatments were generally well-tolerated without significant adverse effects for most children, although we review the reported adverse effects in detail. This review provides evidence for potentially safe and effective treatments for core and associated symptoms of ASD that target underlying known physiological abnormalities associated with ASD. Further research is needed to define subgroups of children with ASD in which these treatments may be most effective as well as confirm their efficacy in DBPC, large-scale multicenter studies.

Mutation of ataxia–telangiectasia mutated is associated with dysfunctional glutathione homeostasis in cerebellar astroglia

“…While the absence of robust neurodegeneration in existing mouse models of A–T has made it difficult to assess the utilization of antioxidant therapies for human A–T in vivo , our findings on isolated A–T astroglia might offer a new cellular tool to evaluate the therapeutic efficacy of different antioxidant approaches to slowing the course of neurological change, and our findings also suggest that NAC or other cysteine precursors might be particularly useful in this regard. It is becoming increasingly apparent that NAC may provide benefit in a variety of neurological conditions, including depression, autism, and treatment of addiction (Asevedo et al ; Dean et al ; Frye and Rossignol ; Ghanizadeh and Moghimi‐Sarani ; Maes et al )), and there has been interest in trials with antioxidants in treatment of A–T. Unfortunately, it appears that none of these trials have used NAC, which our work suggests might be of particular value in such efforts.…”

Increased homocysteine levels correlate with the communication deficit in children with autism spectrum disorder

“…ASD affects approximately 1% of children and is on the rise (MMWR, 2010). There are significant genetic mechanisms underlying these disorders and research studies have uncovered several metabolic abnormalities associated with ASD (Guevara-Campos et al, 2013, 2015Frye and Rossignol, 2014;West et al, 2014). Several clinical trials with different drugs aimed to reduce oxidative stress in ASD patients have been conducted (Frustaci et al, 2012) and the overall studies led to mixed results.…”

Sulforaphane treatment of autism spectrum disorder (ASD)

“…First, extensive evidence shows that sulforaphane counteracts many of the same biochemical and molecular abnormalities associated with ASD, including oxidative stress and reduced antioxidant capacity, defects in glutathione synthesis, mitochondrial dysfunction and low oxidative phosphorylation, increased lipid peroxidation, and neuroinflammation (11)(12)(13)(14)(15)(16). Although it is unclear whether these anomalies are etiological or secondary manifestations, their correction often improves ASD behavior (17).…”