BY THOMAS R. COLLINS
CHICAGO—Autism symptoms were significantly improved in patients taking sulforaphane, a compound found in broccoli and other plants, compared to those taking placebo, according to a preliminary analysis of a phase 2 trial presented here at the Child Neurology Society annual meeting.
In a trial of 50 patients of children, age 3 to 12, six of the 20 patients (30 percent) taking sulforaphane showed improvements on the Ohio Autism Clinical Impressions Scale (OACIS) after 15 weeks. The scale includes questions about social interactions, aberrant behaviors, and other autism domains. That compared with two of 27 (7 percent) who improved on placebo (p=.048), reported Kanwaljit Singh, MD, MPH, instructor of pediatrics at the University of Massachusetts.
The researchers decided to research the compound based on reports that when children with autism had fevers, they got temporarily better — with more eye contact, better sociability, and less irritability.
They focused on sulforaphane, an isothiocyanate found in high concentrations in broccoli sprouts that activates the heat shock response, which also happens in cells during fever. It also has been found to improve mitochondrial dysfunction, and there is evidence that it has an impact on synaptic dysfunction.
A preliminary trial started in 2011, in males age 13 to 27, found that patients taking sulforaphane had improvements of 40- to 50-percent on various aspects of the OACIS scale.
In this latest trial, patients are considerably younger, age 3 to 12. Another important difference is that pure sulforaphane was not used because it is very unstable at room temperature. Instead, investigators gave patients a sulforaphane precursor, glucoraphanin, with the enzyme myrosinase. The enzyme converts the precursor to sulforaphane when it comes into contact with water after being ingested.
Patients on the sulforaphane regimen showed significantly more improvement on the Aberrant Behavior Checklist at 15 weeks (p=.04). But there was no statistically significant difference in change on the Social Responsiveness Scale at any time point, Dr. Singh reported.
The trial included an open-label phase after the initial 15-week blinded phase. The response rate for all patients in the blinded phase was 17 percent, but that tripled in the open-label phase.
Dr. Singh said that during the open-label phase, it's possible that patients and observers were "looking harder for the changes, possibly introducing an element of bias."
In a preliminary biomarker analysis, investigators found an unexpected drop in interleukin-6 (IL-6), a proinflammatory cytokine that is increased during fever.
Commenting on the study, Jean-Baptiste Le Pichon, MD, PhD, associate professor of pediatrics at Children's Mercy Hospital in Kansas City, said that the open-label aspect posed problems for assessing the findings.
"There's so much of a placebo effect that to interpret any of these data is very difficult," he said.
Dr. Le Pichon said that examining sulforaphane based on the observation that children get better when they have a fever is "a reasonable thing." But he said the IL-6 findings — which Dr. Singh had said were a preliminary result and which might change on the final analysis — cast doubt on the reliability of the hypothesis.
"They had a hypothesis, and then they had a result that was completely counterintuitive to the hypothesis that they made," Dr. Le Pichon said. "In other words, they hypothesized that fever makes the kids better, but then they showed that IL-6 goes down when they give the medication. And yet we know very well that IL-6 is one of the interleukins that is responsible for causing the fever."
He said the nature of the disease also makes it difficult to properly assess the findings.
"Autism is an incredibly variable disease, it's caused by a lot of different things."
Drs. Singh and Le Pichon had nothing to disclose.
LINK UP FOR RELATED INFORMATION:
Zimmerman A, Diggins E, Connors S, Singh K. Sulforaphane treatment of children with autism spectrum disorder (ASD) — A progress report (N1.002). Neurology 2018: 90(15 Supplement).