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

Abstract

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.

Microglia and Autism Spectrum Disorder: Overview of Current Evidence and Novel Immunomodulatory Treatment Options

“…Antipurinergic therapy using suramin also proved effective for improving autistic features in fragile X mouse model, showing its efficacy across different etiologic models of ASD 47). More recently, in the first translational pilot trial, low-dose suramin treatment was well tolerated without major adverse effects and associated with significant improvement in core symptoms of ASD in a small number of child and adolescent male patients 48). A study has shown that suramin also inhibits spinal cord microglia activation followed by long-term hyperalgesia 49).…”

Pannexin 1 regulates spiny protrusion dynamics in cortical neurons

“…Crmp2 auto-antibodies have been implicated in ASD (Braunschweig et al, 2013), while suramin treatment corrected synaptic and behavioural phenotypes in the Fragile X mouse model (J. C. Naviaux et al, 2015;R. K. Naviaux et al, 2013R. K. Naviaux et al, , 2017.…”

Metabolic and Behavioral Features of Acute Hyperpurinergia and the Connection to Autism Spectrum Disorder

“…However, the offspring born after an MIA pregnancy have ASD-like features, activated brain microglia, and abnormalities in synapse structure for life [71]. Detailed systems analysis of the MIA model has shown that it recapitulates many of the behavioral [68], metabolic [4], immune, microbiome [72], and brain synaptic features [3,73] of children with ASD. In the past, it was shown that toll-like receptor 3 (TLR3) signaling triggered by poly(IC) was important to induce IL6 and IL17, which in turn played key roles in placental and brain in ammatory signaling that preceded the onset of ASD-like behaviors [74].…”

“…Over the past decade our group has tested a new unifying hypothesis for the origin and treatment of autism spectrum disorder (ASD) in animal models [1][2][3] and a small human clinical trial [4]. This new hypothesis proposes that the behavioral symptoms and neurobiology of ASD are the result of a new kind of metabolic syndrome that arises from abnormalities in purinergic signaling.…”