Abstract

Individuals with autism spectrum disorder (ASD) suffer from developmental disabilities that impact communication, behavior, and social interaction. Immune dysregulation and inflammation have been linked to children with ASD, the latter manifesting in serum levels of macrophage‐derived chemokine (MDC) and thymus, and activation‐regulated chemokine (TARC). Mesenchymal stem cells derived from umbilical cord tissue (UC‐MSCs) have immune‐modulatory and anti‐inflammatory properties, and have been safely used to treat a variety of conditions. This study investigated the safety and efficacy of UC‐MSCs administered to children diagnosed with ASD. Efficacy was evaluated with the Autism Treatment Evaluation Checklist (ATEC) and the Childhood Autism Rating Scale (CARS), and with measurements of MDC and TARC serum levels. Twenty subjects received a dose of 36 million intravenous UC‐MSCs every 12 weeks (four times over a 9‐month period), and were followed up at 3 and 12 months after treatment completion. Adverse events related to treatment were mild or moderate and short in duration. The CARS and ATEC scores of eight subjects decreased over the course of treatment, placing them in a lower ASD symptom category when compared with baseline. MDC and TARC inflammatory cytokine levels also decreased for five of these eight subjects. The mean MDC, TARC, ATEC, and CARS values attained their lowest levels 3 months after the last administration. UC‐MSC administration in children with ASD was therefore determined to be safe. Although some signals of efficacy were observed in a small group of children, possible links between inflammation levels and ASD symptoms should be further investigated. Stem Cells Translational Medicine 2019;8:1008–1016

Lessons Learned

Repeated infusions with umbilical cord mesenchymal stem cells are safe, resulting in only mild or moderate adverse events that are short in duration, with no serious adverse events related to treatment.

Improvements in autism spectrum disorder symptoms and in inflammatory cytokine levels were detected in a small group of children.

These results pave the way for more investigations with umbilical cord stem cells and help establish a novel paradigm for addressing inflammatory‐associated neurological conditions with a safe biological therapy.

Significance Statement

To the authors' knowledge, this is the first single‐arm phase I/II clinical trial of repeated dose umbilical cord mesenchymal stem cells administration in children diagnosed with autism spectrum disorder (ASD). Umbilical cord mesenchymal stem cell infusions were safe and generally well tolerated. Forty percent of children showed notable improvements of symptoms as measured by standardized autism diagnosis tools. Whereas other studies have reported links between inflammatory cytokine levels and ASD, this study only observed a possible link in a small group of children, which merits further investigation.

Full text

Allogeneic Human Umbilical Cord Mesenchymal Stem Cells for the Treatment of Autism Spectrum Disorder in Children: Safety Profile and Effect on Cytokine Levels was originally published in STEM CELLS Translational Medicine Volume 8, Issue 10 and is available on the Stem Cell Journals website.