Annals of Clinical and Translational Neurology
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Research Article

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

Authors

  • Robert K. Naviaux,

    Corresponding author
    1. The Mitochondrial and Metabolic Disease Center, University of California, San Diego School of Medicine, San Diego, California
    2. Department of Medicine, University of California, San Diego School of Medicine, San Diego, California
    3. Department of Pediatrics, University of California, San Diego School of Medicine, San Diego, California
    4. Department of Pathology, University of California, San Diego School of Medicine, San Diego, California

    • Correspondence

      Robert K. Naviaux, The Mitochondrial and Metabolic Disease Center, University of California, San Diego School of Medicine, 214 Dickinson St., Bldg CTF, Rm C102, San Diego, CA 92103-8467. Tel: 619-543-2904; Fax: 619-543-7868; E-mail: Naviaux@ucsd.edu

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  • Brooke Curtis,

    1. Alliant International University, San Diego, California
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  • Kefeng Li,

    1. The Mitochondrial and Metabolic Disease Center, University of California, San Diego School of Medicine, San Diego, California
    2. Department of Medicine, University of California, San Diego School of Medicine, San Diego, California
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  • Jane C. Naviaux,

    1. The Mitochondrial and Metabolic Disease Center, University of California, San Diego School of Medicine, San Diego, California
    2. Department of Neurosciences, University of California, San Diego School of Medicine, La Jolla, CA
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  • A. Taylor Bright,

    1. The Mitochondrial and Metabolic Disease Center, University of California, San Diego School of Medicine, San Diego, California
    2. Department of Medicine, University of California, San Diego School of Medicine, San Diego, California
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  • Gail E. Reiner,

    1. The Mitochondrial and Metabolic Disease Center, University of California, San Diego School of Medicine, San Diego, California
    2. Department of Neurosciences, University of California, San Diego School of Medicine, La Jolla, CA
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  • Marissa Westerfield,

    1. The Research in Autism and Development Laboratory (RAD Lab), University of California, La Jolla, CA
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  • Suzanne Goh,

    1. Pediatric Neurology Therapeutics, San Diego, CA
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  • William A. Alaynick,

    1. The Mitochondrial and Metabolic Disease Center, University of California, San Diego School of Medicine, San Diego, California
    2. Department of Medicine, University of California, San Diego School of Medicine, San Diego, California
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  • Lin Wang,

    1. The Mitochondrial and Metabolic Disease Center, University of California, San Diego School of Medicine, San Diego, California
    2. Department of Medicine, University of California, San Diego School of Medicine, San Diego, California
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  • Edmund V. Capparelli,

    1. Department of Pediatrics, and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego School of Medicine, La Jolla, CA
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  • Cynthia Adams,

    1. Clinical and Translational Research Institute (CTRI), University of California, San Diego, La Jolla, CA, 92037
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  • Ji Sun,

    1. Clinical and Translational Research Institute (CTRI), University of California, San Diego, La Jolla, CA, 92037
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  • Sonia Jain,

    1. Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, CA, 92093
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  • Feng He,

    1. Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, CA, 92093
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  • Deyna A. Arellano,

    1. Clinical and Translational Research Institute (CTRI), University of California, San Diego, La Jolla, CA, 92037
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  • Lisa E. Mash,

    1. The Research in Autism and Development Laboratory (RAD Lab), University of California, La Jolla, CA
    2. Department of Psychology, San Diego State University, San Diego, CA
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  • Leanne Chukoskie,

    1. The Research in Autism and Development Laboratory (RAD Lab), University of California, La Jolla, CA
    2. Institute for Neural Computation, University of California, 9500 Gilman Drive, La Jolla
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  • Alan Lincoln,

    1. Alliant International University, San Diego, California
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  • Jeanne Townsend

    1. Department of Neurosciences, University of California, San Diego School of Medicine, La Jolla, CA
    2. The Research in Autism and Development Laboratory (RAD Lab), University of California, La Jolla, CA
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Abstract

Objective

No 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.

Methods

Ten 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.

Results

Blood 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.

Interpretation

The 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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Ancillary

Article Information

DOI

10.1002/acn3.424

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© 2017 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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Publication History

  • Issue online:
  • Version of record online:
  • Manuscript Accepted:
  • Manuscript Revised:
  • Manuscript Received:

Funded by

  • William Wright Family Foundation
  • UCSD Christini Fund
  • Autism Research Institute (ARI)
  • Lennox Foundation
  • Gupta Family and Satya Fund
  • Agrawal Family
  • N of One Autism Research Foundation
  • Rodakis Family
  • Guts Foundation
  • UCSD Mitochondrial Disease Research Fund
  • Dr. Elizabeth Mumper Cooper
  • Daniel and Kelly White Family
  • Jane Botsford Johnson Foundation

Supporting Information

FilenameDescription
acn3424-sup-0001-Supinfo.pdfPDF document, 2094K

Table S1. Single-dose suramin pharmacokinetics.

Table S2. Suramin pharmacometabolomics. Pathways changed at 2 days.

Table S3. Suramin pharmacometabolomics. Metabolites changed at 2 days.

Table S4. Suramin pharmacometabolomics. Metabolites changed at 6 weeks.

Figure S1. Storyboard illustration of each step of the infusion day visit.

Figure S2. Suramin pharmacometabolomics. Rank order of metabolites and pathways that were changed by suramin at 2 days after treatment.

Figure S3. Suramin pharmacometabolomics pathway visualization. (A) After 2 days. (B) After 6 weeks. Metabolites indicated in red were increased, and those in green were decreased compared to controls (see z-score scale in upper right).

Figure S4. Outcomes. (A) 6 Weeks ADOS comparison scores by two-way ANOVA. (B) 6 Weeks ADOS comparison score improvement after suramin. (C) 6 Weeks ADOS social affect score improvement after suramin. (D) 6 Weeks ADOS restricted and repetitive behavior score improvement after suramin. (E) 2 days ADOS comparison scores were not changed. (F) no change in 6 weeks ADOS scores in subjects receiving saline placebo. (G) no change in 6 weeks ADOS social affect scores in subjects receiving placebo. (H) no change in 6 weeks ADOS restricted and repetitive behavior scores in subjects receiving placebo. (I) no change in 6 weeks Expressive One-Word Picture Vocabulary scores. (J) 7-day improvement in ABC stereotypy scores after suramin. (K) 6-week Improvement in ABC stereotypy scores after suramin. (L) 7-day Improvement in ATEC total scores after suramin. (M) no change in 6 weeks EOWPVT scores after saline. (N) no change in 7 days ABC stereotypy scores after saline. (O) no change in 6 weeks ABC stereotypy scores after saline. (P) no change in 7 days ATEC total scores after saline. (Q) improved ATEC speech, language, and communication scores 7 days after suramin. (R) improved ATEC sociability scores 7 days after suramin. (S) improved ATEC speech, language, and communication scores 6 weeks after suramin. (T) improved ADOS comparison scores after dropping a subject who missed the 6-week visit (N = 4). (U) no change in 7 days ATEC speech, language, and communication after saline. (V) no change in 7 days ATEC sociability after saline. (W) no change in 6 weeks ATEC speech, language, and communication scores 6 weeks after saline (X) no change in EOWPVT scores after dropping subject who missed the 6-week visit (N = 4). (Y) no change in 2 days ADOS scores after suramin. (Z) no change in 6 weeks RBQ total scores after suramin. (aa) improved core symptoms of ASD and other behaviors by CGI at 6 weeks after suramin. P values: *0.05, **0.01, ***0.001. (bb) Top 3, most changed symptoms named by parents in the 6-week CGI. (cc) no change in 2 days ADOS scores after saline. (dd) no change in 6 weeks RBQ total scores after saline.

Data S1. Clinical Global Impression (CGI) questionnaire.

Data S2. Social Stories to Accompany the Storyboard Panels Describing Each Step of the Infusion Day Visit.

Please note: Wiley-Blackwell is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

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  • Number of times cited: 2
  1. 1Valsamma Eapen, Laura Nicholls, Vanessa Spagnol, Nisha E. Mathew, Current status of biological treatment options in Autism Spectrum Disorder, Asian Journal of Psychiatry, 2017, 30, 1CrossRef
  2. 2Haruhiro Higashida, Teruko Yuhi, Shirin Akther, Sarwat Amina, Jing Zhong, Mingkun Liang, Tomoko Nishimura, Hong-Xiang Liu, Olga Lopatina, Oxytocin release via activation of TRPM2 and CD38 in the hypothalamus during hyperthermia in mice: Implication for autism spectrum disorder, Neurochemistry International, 2017CrossRef