Randomized clinical trial of low dose suramin intravenous infusions for treatment of autism spectrum disorder

David Hough; Alice R Mao; Michael Aman; Reymundo Lozano; Constance Smith-Hicks; Veronica Martinez-Cerdeno; Michael Derby; Zachary Rome; Niel Malan; Robert L Findling

doi:10.1186/s12991-023-00477-8

Randomized clinical trial of low dose suramin intravenous infusions for treatment of autism spectrum disorder

Ann Gen Psychiatry. 2023 Nov 6;22(1):45. doi: 10.1186/s12991-023-00477-8.

Authors

Affiliations

¹ PaxMedica, Inc, sponsor of the study, 303 S Broadway, Suite 125, Tarrytown, NY, 10591, USA. psychsvcprince@gmail.com.
² Psychiatry and Behavioral Sciences, Baylor College of Medicine and PaxMedica, Inc., Houston, Texas, USA.
³ O.S.U. Research Unit on Pediatric Psychopharmacology (RUPP), Research, Nisonger Center at The Ohio State University, Columbus, Ohio, USA.
⁴ Genetics and Genomics Sciences, Psychiatry and Pediatrics, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
⁵ Director of Fragile X Syndrome Clinical at Mount Sinai Hospital, New York City, New York, USA.
⁶ Neurology, Kennedy Krieger Institute, Johns Hopkins Univ School of Medicine, Baltimore, MD, USA.
⁷ Pathology and Laboratory Medicine, Anatomy of Autism and FXS laboratory, Institute for Pediatric Regenerative Medicine, Shriners Hospital of Northern California, and UCD MIND Institute. Pathology Director of the FXS & FXTAS brain repository at UCD, University of California Davis School of Medicine, Davis, California, USA.
⁸ Tardimed Sciences LLC., PaxMedica, Inc., Tarrytown, New York, USA.
⁹ PaxMedica, Inc., Tarrytown, New York, USA.
¹⁰ Phoenix Pharma LTD, 2 Eastbourne Rd, Mt Croix, Port Elizabeth, South Africa.
¹¹ Chair, Department of Psychiatry, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA.

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.

Clinicaltrials: Gov registration ID is NCT06058962, last update posted 2023-09-28.

Keywords: Autism spectrum disorder; Purinergic receptor antagonist; Suramin.

Associated data

ClinicalTrials.gov/NCT06058962

Grants and funding

P50 HD103538/HD/NICHD NIH HHS/United States