Improving symptoms of autism in young children has been the focus of many studies in recent years, and the research groups in the Marcus Center for Cellular Cures and the Duke Center for Autism and Brain Development, led by Drs. Joanne Kurtzberg and Geraldine Dawson, have been attempting to use intravenous infusions of cord blood as a means for improvement. The Duke ACT project had an initial study published in Stem Cells Translational Medicine in 2017. That study focused on 25 children, aged 2-6 years, and found noticeable improvement from autologous cord blood infusions for children with one or more core symptoms of autism. It also showed that the infusions of cord blood from the best cord blood banks were safe.

Background of the Duke ACT Study

Every study has to follow strict rules in order to provide accurate results. The Duke ACT study was a randomized, double blinded, placebo controlled, prospective, crossover study testing the ability for core blood infusions to improve core symptoms of autism in 180 children. Eligibility for the study required candidates to be between ages 2-7, to have a confirmed diagnosis of ASD without a known genetic cause of ASD, to be English speaking, and to be without other confounding illnesses. Children also had to have negative results for Fragile-X, and a negative chromosomal microarray.

Results from the initial Duke ACT Study showed that the most improvement was within children with non-verbal IQ >70 after an autologous cord blood infusion, so children were screened remotely for cognitive function, attempting to include only children with nonverbal IQ>70. Children were not turned away, however, if remote screening and on-site IQ test results differed. The study included 180 children with a minimum expectation of 143 meeting requirements of NVIQ>70, but only 101 children ended up meeting criteria.

ACT Study Design

The 180 enrolled children were separated between treatment and placebo arms, and were stratified further by age and non-verbal IQ. For the first infusion, 120 received cord blood (split between autologous, and allogeneic) from the best cord blood banks, and 60 received placebo. Results were taken 6 months after. For second infusion, the children crossed over, receiving the opposite, then results were taken again after 6 months. Those testing and administering were isolated (therefore done blindly).

Results for Safety

Throughout the study, there were no significant severe adverse effects. Mild infusion site reactions were observed, including hives, cough, or wheezing in 4/61 of the placebo group, 2/56 of the autologous cord blood group, and 3/63 of the allogeneic cord blood group. All were resolved with additional treatments of Benadryl, albuterol, and/or a second dose of solumedrol. Mild and transient anxiety was also reported, but it did not differ between groups.

Effectiveness Results of Using the Best Cord Blood Banks

The study did show significant improvements in the cord blood group for the subset of children in the study who were 4-7 years of age and were without intellectual disability with NVIQ>70. The Duke ACT study did not show a benefit of cord blood over placebo on VABS-3 socialization scale from parent reported outcomes. As well, since only 101 of the 180 children ended up being NVIQ>70 the analysis in general was flawed, as 143 were the minimum required. Improvements were seen in communication (VABS-3), attention (eye tracking), and increased alpha and beta EEG power. On the Clinical Global Impression-Improvement scale, only allogeneic cord blood receiving children showed improvement compared to placebo, however they received a higher dose of total cells, so it’s unknown whether the advantage over autologous was due to increased dose or donor cell source.

Overall, the results for the Duke ACT study are promising; however, future trials will need to limit children to NVIQ>70 for more accurate results by ensuring only those that pass the on-site IQ measurement test are enrolled. As well, due to the large placebo effect, a larger sample size will be used in future studies, and a need for a concomitant placebo-control, cross-over arm. Future tests are planned to test the population of children used with cord blood infusions from the best cord blood banks as well. Visit our website for more details.

Reviewed by Paul V. Holland, MD