Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: Part B - Behavioral results

Authors:
Adams, J.B., Baral, M., Geis, E., Mitchell, J., Ingram, J., Hensley, A., Zappia, I., Newmark, S., Gehn, E., Rubin, R.A. and Mitchell, K.

https://pubmed.ncbi.nlm.nih.gov/19852790/

doi: 10.1186/1472-6904-9-17

Summary of study

The study suggests that oral DMSA therapy may reduce behavioral symptoms in children with ASD, particularly in those with elevated toxic metal levels. The 7-round treatment showed a stronger correlation with metal excretion and glutathione improvements, supporting a potential biological effect. However, limitations such as an unclear dosing regimen, lack of a true placebo control, and mixed outcomes for some participants highlight the need for further research to validate and optimize this approach.

Findings

• Behavioral Improvements:

  • Both groups in the study—the "1-round" group (one round of DMSA followed by six rounds of placebo) and the "7-round" group (seven rounds of DMSA)—demonstrated significant improvements in behavioral symptoms of autism. These improvements were assessed using multiple tools:

    • ATEC (Autism Treatment Evaluation Checklist): The 7-round group improved by 26%, while the 1-round group improved by 19%. The difference between groups was not statistically significant.

    • PDD-BI (Pervasive Developmental Disorder Behavior Inventory): Both groups showed a 24% improvement in modified composite scores for maladaptive behaviors.

    • SAS (Severity of Autism Scale): Improvements were 19% for the 7-round group and 18% for the 1-round group, with no significant difference.

    • ADOS (Autism Diagnostic Observation Schedule): The 7-round group showed slightly better improvements (e.g., 10% in sociability), but these were not statistically significant compared to the 1-round group.

    • PGI (Parent Global Impressions): Both groups reported similar improvements (e.g., 1.7 vs. 1.6 on the overall score), with no significant differences.

  • Overall, approximately 77% of participants showed improved autism severity scores, 12% showed no change, and 11% experienced a slight worsening.

• Correlation with Metal Excretion and Glutathione:

  • In the 7-round group, improvements in behavioral symptoms (particularly in PDD-BI and ATEC) were strongly correlated with the urinary excretion of toxic metals (e.g., thallium, arsenic, lead, mercury) and improvements in glutathione levels. The regression analysis showed high adjusted R² values (e.g., 0.75 for PDD-BI), suggesting a real biological effect rather than a placebo effect.

  • For the 1-round group, no significant correlations were found, indicating that their improvements might be due to other factors, such as a placebo effect or natural progression.

• Age Effects:

  • Improvements were observed across different ages, with older children improving as much or nearly as much as younger children, indicating that age did not significantly influence the outcomes.

• Gut Symptoms:

  • No significant changes in gut problems (e.g., diarrhea) were observed. There was a slight, non-significant increase in constipation, suggesting that DMSA therapy did not generally exacerbate gut issues.

Type of Chelator Used

• Chelator: The study used oral DMSA (Dimercaptosuccinic Acid), a chelating agent FDA-approved for treating lead poisoning in children as young as 2 years. In this study, it was applied off-label to children with ASD who showed evidence of significant heavy metal exposure based on urinary excretion after a DMSA challenge.

Dose

• Dose Details: The exact dose of DMSA (e.g., mg/kg) is not specified in the document. The study describes the administration as follows:

  • Phase 1: A screening round consisting of nine doses over three days (likely three doses per day).

  • Phase 2: For the 7-round group, six additional rounds were administered after the screening round, while the 1-round group received placebo for these six rounds.

  • The specific dosage per administration is not provided and is likely detailed in the accompanying paper (reference [6]), which is not available here. Without this, it’s assumed the dose might align with standard protocols for lead poisoning (e.g., 10 mg/kg three times daily), but this is not confirmed in the text.

Time Until Symptoms Improved

• Time Frame: The exact duration until symptoms improved is not explicitly stated, as the total length of the study and intervals between rounds are not specified.

  • Study Design: Behavioral improvements were assessed at the end of Phase 2, which followed the initial screening round (Phase 1). Phase 1 involved one round (three days), and Phase 2 involved six additional rounds for the 7-round group. Each round is noted as nine doses over three days, suggesting each round lasted three days.

  • Inference: The improvements were observed by the end of Phase 2, which could span several weeks or months depending on rest periods between rounds (common in chelation therapy, e.g., 3 days on, 11 days off), but this is not detailed. Thus, the time until symptoms improved is the duration of Phase 2, an unspecified period following the initial three-day screening round.