Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism

James, S. Jill; Cutler, Paul; Melnyk, Stepan; Jernigan, Stefanie; Janak, Laurette; Gaylor, David W.; Neubrander, James

doi:10.1093/ajcn/80.6.1611

Cited by 826 publications

(759 citation statements)

References 54 publications

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“…54,55 In addition, alternative practitioners have been discussing the theory that anti-oxidant pathways are insufficient in patients with autism. This relationship has been noted in the past, and evidence of a predisposition of insufficient glutathione or anti-oxidant reserves in autistic patients has been described by James et al 56,57 Chez 58 previously reported a similar insufficiency in antioxidant protection in patients diagnosed with variants of Landau-Kleffner and concurrent autistic features. Insufficient anti-oxidant protection may not be the initial cause, but rather an endpoint of chronic ongoing inflammation.…”

Section: Human Evidence Of Ongoing Atypical Inflammatory Responsesupporting

confidence: 52%

Immune Therapy in Autism: Historical Experience and Future Directions with Immunomodulatory Therapy

Chez

Guido-Estrada

2010

Neurotherapeutics

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Summary: Autism affects 1 in 110 new births, and it has no single etiology with uniform agreement. This has a significant impact on the quality of life for individuals who have been diagnosed with autism. Although autism has a spectrum quality with a shared diagnosis, it presents a uniquely different clinical appearance in each individual. Recent research of suspected immunological factors have provided more support for a probable immunological process or for processes that may play a role in the acquisition of an autistic condition. These factors include prenatal, genetic, and postnatal findings, as well as the discovery of a dysfunctional chronic pro-inflammatory state in brain tissue and cerebrospinal fluid in subsets of autistic patients. These findings offer new theories that may lead to the development of disease modification or preventative therapeutic options in the near future. This article reviews prenatal, genetic, and observed immune aspects of the autism condition that may be risk factors in the presentation of the autistic clinical phenotype. Historical immune interventions in autism are reviewed and potential new therapies and interventions are discussed.

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Section: Human Evidence Of Ongoing Atypical Inflammatory Responsesupporting

confidence: 52%

Immune Therapy in Autism: Historical Experience and Future Directions with Immunomodulatory Therapy

Chez

Guido-Estrada

2010

Neurotherapeutics

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“…The transfer of methyl groups is an important reaction in this metabolic pathway, and some hypothesize that oxidative stress and toxicity are responsible for the neuronal insult involved in ASD. 126 Abnormal metabolic profiles and impaired methylation have been reported in some children with ASD, 127,128 although no behavioral correlations were investigated. There are no randomized controlled trials published regarding the efficacy of molecules in this pathway on symptoms of ASD.…”

Section: Biologically Based Practicesmentioning

confidence: 99%

Complementary and Alternative Medicine in Autism: An Evidence-Based Approach to Negotiating Safe and Efficacious Interventions with Families

2010

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Summary: This review focuses on helping clinicians identify resources and develop strategies they may use to effectively negotiate safe and effective use of complementary and alternative medicine (CAM) treatments with families of children with autism spectrum disorders (ASD), as well as other neurodevelopmental disorders. Since new types of CAM continue to be introduced into the autism community, emphasis is placed on providing clinicians with tools to help families negotiate the myriad of available treatments and make decisions based on current safety and efficacy data, while remaining mindful of the reasons families may be considering these treatments.We familiarize readers with high-quality, evidence-based resources that providers and families may use to ascertain current information about specific types of CAM, verify the content of biologically-based treatments, identify ongoing CAM research and obtain toolkits designed to help healthcare providers raise the topic of CAM usage and facilitate disclosure and discussion of CAM use with patients and their families. Key Words: Complementary and alternative medicine, autism, integrative medicine, gluten-free casein-free diet, melatonin, chelation, hyperbaric oxygen treatment, evidence-based medicine.

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“…The formulation of the cell danger hypothesis was based on the recognition that similar metabolic pathways were coordinately regulated as an adaptive response to cellular threat regardless of whether the perturbation was caused by a virus,15 a bacterium,16 genetic forms of mitochondrial disease,10 or neurodevelopmental disorders with complex gene–environment pathogenic mechanisms like autism 17. These metabolic pathways traced to mitochondria.…”

Section: Introductionmentioning

confidence: 99%

Low‐dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial

Naviaux

Curtis

et al. 2017

Ann Clin Transl Neurol

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ObjectiveNo drug is yet approved to treat the core symptoms of autism spectrum disorder (ASD). Low‐dose suramin was effective in the maternal immune activation and Fragile X mouse models of ASD. The Suramin Autism Treatment‐1 (SAT‐1) trial was a double‐blind, placebo‐controlled, translational pilot study to examine the safety and activity of low‐dose suramin in children with ASD.MethodsTen male subjects with ASD, ages 5–14 years, were matched by age, IQ, and autism severity into five pairs, then randomized to receive a single, intravenous infusion of suramin (20 mg/kg) or saline. The primary outcomes were ADOS‐2 comparison scores and Expressive One‐Word Picture Vocabulary Test (EOWPVT). Secondary outcomes were the aberrant behavior checklist, autism treatment evaluation checklist, repetitive behavior questionnaire, and clinical global impression questionnaire.ResultsBlood levels of suramin were 12 ± 1.5 μmol/L (mean ± SD) at 2 days and 1.5 ± 0.5 μmol/L after 6 weeks. The terminal half‐life was 14.7 ± 0.7 days. A self‐limited, asymptomatic rash was seen, but there were no serious adverse events. ADOS‐2 comparison scores improved by −1.6 ± 0.55 points (n = 5; 95% CI = −2.3 to −0.9; Cohen's d = 2.9; P = 0.0028) in the suramin group and did not change in the placebo group. EOWPVT scores did not change. Secondary outcomes also showed improvements in language, social interaction, and decreased restricted or repetitive behaviors.InterpretationThe safety and activity of low‐dose suramin showed promise as a novel approach to treatment of ASD in this small study.

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Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism

Abstract: An increased vulnerability to oxidative stress and a decreased capacity for methylation may contribute to the development and clinical manifestation of autism.

Cited by 826 publications

References 54 publications

Immune Therapy in Autism: Historical Experience and Future Directions with Immunomodulatory Therapy

Immune Therapy in Autism: Historical Experience and Future Directions with Immunomodulatory Therapy

Complementary and Alternative Medicine in Autism: An Evidence-Based Approach to Negotiating Safe and Efficacious Interventions with Families

Low‐dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial

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