Language

English

Publication Date

11-6-2023

Journal

Annals of General Psychiatry

DOI

10.1186/s12991-023-00477-8

PMID

37932739

PMCID

PMC10626700

PubMedCentral® Posted Date

11-6-2023

PubMedCentral® Full Text Version

Post-print

Abstract

Background: There is a critical need for effective treatment of the core symptoms of autism spectrum disorder (ASD). The purinergic antagonist suramin may improve core symptoms through restoration of normal mitochondrial function and reduction of neuro-inflammation via its known antagonism of P2X and P2Y receptors. Nonclinical studies in fragile X knockout mice and the maternal immune activation model support these hypotheses.

Methods: We conducted a 14 week, randomized, double-blind, placebo-controlled proof -of-concept study (N = 52) to test the efficacy and safety of suramin intravenous infusions in boys aged 4-15 years with moderate to severe ASD. The study had 3 treatment arms: 10 mg/kg suramin, 20 mg/kg suramin, and placebo given at baseline, week 4, and week 8. The Aberrant Behavior Checklist of Core Symptoms (ABC-Core) (subscales 2, 3, and 5) was the primary endpoint and the Clinical Global Impressions-Improvement (CGI-I) was a secondary endpoint.

Results: Forty-four subjects completed the study. The 10 mg/kg suramin group showed a greater, but statistically non-significant, numeric improvement (- 12.5 ± 3.18 [mean ± SE]) vs. placebo (- 8.9 ± 2.86) in ABC-Core at Week 14. The 20 mg/kg suramin group did not show improvement over placebo. In exploratory analyses, the 10 mg/kg arm showed greater ABC Core differences from placebo in younger subjects and among those with less severe symptoms. In CGI-I, the 10 mg/kg arm showed a statistically significant improvement from baseline (2.8 ± 0.30 [mean ± SE]) compared to placebo (1.7 ± 0.27) (p = 0.016). The 20 mg/kg arm had a 2.0 ± 0.28 improvement in CGI-I, which was not statistically significant compared to placebo (p = 0.65).

Conclusion: Suramin was generally safe and well tolerated over 14 weeks; most adverse events were mild to moderate in severity. Trial Registration Registered with the South African Health Authority, registration number DOH-27-0419-6116.

Keywords

Autism spectrum disorder, Suramin, Purinergic receptor antagonist

Comments

Trial Registration Registered with the South African Health Authority, registration number DOH-27–0419-6116. ClinicalTrials.Gov registration ID is NCT06058962, last update posted 2023–09-28.

Published Open-Access

yes

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