Autism spectrum disorder (ASD) is a childhood developmental disorder that impacts language abilities and social interactions, and can cause involuntary, repetitive behavior. In the United States, about 1 in 59 children is currently affected by ASD. An exact cause of ASD still has not been discovered. However, some research suggests that a dysfunctional immune system may play a role in the development of some cases of ASD. This immune dysfunction may cause inflammation in the brain, which may cause damage within the nervous system and developing brain.[1 ,3] Because of this finding, there is interest in identifying treatments that could calm this type of immune response.
Cells found in umbilical cord blood have unique properties. Research has shown that cord blood may be able to modulate immune responses, reduce inflammation, and stimulate the repair of tissue as well as travel to sites of neurological injury.[4, 5] Because of these properties, cord blood may be a potential therapy for ASD. In the last few years, clinical trials have been attempting to assess the therapeutic value of newborn stem cells in the treatment of ASD. Here we summarize the completed clinical trials and describe some of the ongoing studies in the United States.
The first clinical trial published utilizing cord blood for ASD was a phase I open label trial from researchers at Duke University. This study, published in April 2017, included 25 children ages 2 to 6 with a diagnosis of ASD who all received a single dose of their own cord blood. The aims of the study were to assess the safety of a single, intravenous autologous cord blood infusion for children with ASD and to determine whether various behavioral and functional assessments would be valuable endpoints in future studies. Participants underwent the behavioral and functional assessments prior to infusion, 6 months post infusion, and 12 months post infusion. The study found that autologous cord blood infusions were safe and feasible for the study population. While not designed to assess efficacy, the researchers did note that significant improvements in behavior were seen in multiple outcome measures used for the study at 6 months post infusion and those improvements were sustained at 12 months post infusion. Also due to the design of the study, it was not possible to determine whether the improvements seen were caused by the treatment or if they were a result of the natural progression of the children over time. Importantly, this study laid the groundwork for future clinical trials using newborn stem cells as a potential therapy for children with ASD.
Since the initial publication of the open label trial, Duke has also published two papers describing secondary outcomes from EEGs and MRIs performed on the 25 participants. In August 2018, results of electroencephalography (EEG) data were published. EEGs measure the electrical activity in the brain over a period of time, using small electrodes attached to the scalp. When different groups of neurons fire, they produce distinct patterns of electrical activity, also known as brain waves. The distinct patterns of the brain waves are useful for diagnosing sleep disorders and conditions like epilepsy. Researchers have noted that children with ASD exhibit patterns of EEG activity that are visibly different from those of children without an ASD diagnosis. In this study, EEG testing was performed before the children were given the initial cord blood infusions and at their 6 and 12 month follow-up appointments. Characteristics of the EEG that have previously been associated with ASD shifted toward a more normal pattern on the 12 month post infusion EEG data in this study and these results were statistically significant. These results could not only help researchers understand how the brain changes after cord blood therapy, but also suggest that EEGs could potentially help us identify which children will respond well to cord blood treatment before they are treated.
Similarly, results of the magnetic resonance imaging (MRI) data collected on the initial Duke cohort were published in January 2019. Individuals with ASD are known to have different patterns of white matter development than individuals without ASD, but the mechanism underlying these changes remains unknown. There is also evidence to suggest that neuroinflammation is linked to changes in brain connectivity. This publication compared the MRIs performed before autologous cord blood infusion to those performed at the 6-month post infusion follow-up appointment. The hypothesis was that the behavioral improvements observed in the initial publication would correlate with changes to the white matter brain connectivity as seen on MRI in areas of the brain known to be abnormal in children with ASD. This hypothesis was confirmed as improved connectivity in frontal, temporal, and specific subcortical regions did correlate with improvements in behavior in this study. While these data are exciting, it is important to remember that this is still based on the initial open-label trial and further placebo-controlled studies are necessary to determine whether the types of changes observed are caused by the cord blood infusions or coincident developmental changes.
The first placebo-controlled study in the United States to test cord blood as a potential treatment for autism was published in February 2018. In this study, 30 children received either an infusion of their own cord blood or a saline placebo at the beginning of the study. After 24 weeks, participants received the opposite product and were followed for an additional 24 weeks. The aims of the study were to assess safety and preliminary treatment effectiveness. The study demonstrated that an infusion of a child’s own cord blood was safe and feasible. Although some of the children who participated in the study demonstrated verbal and behavioral improvements, the cohort as a whole did not show statistically significant improvements. Researchers were not able to determine whether cord blood was beneficial in this trial, but further research to see if cord blood may be an effective treatment for ASD is warranted.
Though the published clinical trials are promising, larger, well-controlled clinical trials are necessary to determine whether umbilical cord blood is efficacious in the treatment of ASD. Researchers at Duke University are currently working on a large double-blind, placebo-controlled study of a single autologous or allogeneic, unrelated cord blood infusion in children ages 2-7 years with a diagnosis of ASD. Participants will either receive infusion of cord blood cells or placebo at baseline followed by an infusion six months later of the opposite product so that all participants are treated with cord blood at some point in the study. Patients without a suitable autologous cord blood unit will receive cells from a HLA- and ABO-matched unrelated donor unit from the Carolinas Cord Blood Bank. Enrollment of >165 participants is complete and the study is ongoing with an estimated completion date in 2019.
In addition to ongoing research evaluating the use of umbilical cord blood as a treatment for ASD, researchers at Duke are also evaluating the use of mesenchymal stem cells (MSCs) derived from umbilical cord tissue for ASD treatment based on some evidence that suggests that these cells may better modulate the immune system. Currently, there is a phase I, open-label trial to assess the safety of one, two, and three intravenous doses of human cord tissue derived mesenchymal stem cells (hCT-MSCs) in children ages 2-11 years with a diagnosis of ASD. Three patients will receive a single dose of hCT-MSCs, three patients will receive two doses of hCT-MSCs given two months apart, and six patients will receive three doses of hCT-MSCs each given two months apart. The primary outcome is safety, but ASD outcome measures will be assessed at baseline and six months from baseline. The estimated completion date for this study is 2019.
As research utilizing umbilical cord blood and tissue for the treatment of ASD continues, we look forward to results from larger placebo-controlled clinical trials to determine the efficacy of these treatments. Even if efficacy is established, we will still have more to learn about the best dosing and timing of treatments. It is important to be cautiously optimistic when relaying information about these potential therapies to families since these are experimental therapies and we have much more to learn, but the results from initial clinical trials are exciting and we are hopeful for the possibilities of utilizing newborn stem cells in the treatment of ASD.
- Gupta S, Aggarwal S, Heads C. Dysregulated immune system in children with autism: beneficial effects of intravenous immune globulin on autistic characteristics. Journal of Autism and Developmental Disorders. 1996 Aug; 26 (4):439-452.
- Centers for Disease Control and Prevention. Accessed March 22, 2019. https://www.cdc.gov/ncbddd/autism/data.html.
- Goines P and Van de Water J. The immune system’s role in the biology of autism. Current Opinion in Neurology. 2010 April 23; 111-117. doi:10.1097/WCO.0b013e3283373514.
- Sun JM, Kurtzberg J. Cord blood for brain injury. Cytotherapy. 2015 June; 17 (6):775-785. doi:10.1016/j.jcyt.2015.03.004.
- Lv YT, Zhang Y, Liu M, Qiuwaxi JN, Ashwood P, Cho SC, Huan Y, Ge RC, Chen XW, Wang ZJ, Kim BJ, Hu X. Transplantation of human cord blood mononuclear cells and umbilical cord-derived mesenchymal stem cells in autism. Journal of Translational Medicine. 2013 Aug 27; 11:196. doi:10.1186/1479-5876-11-196.
- Dawson G, Sun JM, Davlantis KS, Murias M, Franz L, Troy J, Simmons R, Sabatos-DeVito M, Durham R, Kurtzberg J. Autologous cord blood infusions are safe and feasible in young children with autism spectrum disorder: Results of a single-center phase I open-label trial. Stem Cells Translational Medicine. 05 April 017; 6 (5): 1332-1339. https://doi.org/10.1002/sctm.16-0474
- Murias M, Major S, Compton S, Buttinger J, Sun JM, Kurtzberg J, Dawson G. Electrophysiological Biomarkers Predict Clinical Improvement in an Open‐Label Trial Assessing Efficacy of Autologous Umbilical Cord Blood for Treatment of Autism. Stem Cells Translational Medicine. 01 August 2018; 7(11):783-791. https://doi.org/10.1002/sctm.18-0090
- Carpenter KLH, Major S, Tallman C, Chen LW, Franz L, Sun J, Kurtzberg J, Song A, Dawson G. White Matter Tract Changes Associated with Clinical Improvement in an Open‐Label Trial Assessing Autologous Umbilical Cord Blood for Treatment of Young Children with Autism. Stem Cells Translational Medicine. 08 January 2019; 8(2):138-147. https://doi.org/10.1002/sctm.18-0251
- Chez MG, Guido-Estrada N.(2010). Immune therapy in autism: historical experience and future directions with immunomodulatory therapy. Neurotheraputics, 7(3):293-301.
- Chez M, Lepage C, Parise C, Dang-Chu A, Hankins A, Carroll M. Safety and observations from a placebo-controlled, crossover study to assess use of autologous umbilical cord blood stem cells to improve symptoms in children with autism. Stem Cells Translational Med. 2018 Feb 6. http://dx.doi.org/10.1002/sctm.17-0042
- Cord Blood Infusion for Children with Autism Spectrum Disorder (Duke ACT). Accessed March 22, 2019. https://clinicaltrials.gov/ct2/show/NCT02847182.
- hCT-MSCs for Children with Autism Spectrum Disorder (ASD) (hCT-MSCs). Accessed March 22, 2019. https://clinicaltrials.gov/ct2/show/NCT03099239
Michelle McDougle, MS, CGC is a Clinical Science Liaison for CBR and educates healthcare providers about umbilical cord blood and cord tissue banking as well as current and potential future uses of stem cells in medicine.
Michelle is a genetic counselor by training and after graduating with a Master of Science in Genetic Counseling degree from UT Health Science Center at Houston, she started a prenatal genetic counseling practice at WellStar Health System outside of Atlanta, GA. After working closely with genetic testing laboratory partners to boost genetic counseling referrals to her clinic, Michelle was offered a Medical Science Liaison position with Ariosa Diagnostics/Roche Diagnostics Corporation supporting the Harmony Prenatal Test in the Southeast. In this role, Michelle presented information about noninvasive prenatal testing (NIPT) in both formal and non-formal meetings with healthcare providers and spoke at many regional genetics and OBGYN conferences.
Now, in her role at CBR, Michelle pulls from her training as a genetic counselor and experience working with prenatal patients to ensure that women’s health providers feel confident in discussing the amazing potential of newborn stem cells.