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

Abstract

Despite advances in early diagnosis and behavioral therapies, more effective treatments for children with autism spectrum disorder (ASD) are needed. We hypothesized that umbilical cord blood‐derived cell therapies may have potential in alleviating ASD symptoms by modulating inflammatory processes in the brain. Accordingly, we conducted a phase I, open‐label trial to assess the safety and feasibility of a single intravenous infusion of autologous umbilical cord blood, as well as sensitivity to change in several ASD assessment tools, to determine suitable endpoints for future trials. Twenty‐five children, median age 4.6 years (range 2.26–5.97), with a confirmed diagnosis of ASD and a qualified banked autologous umbilical cord blood unit, were enrolled. Children were evaluated with a battery of behavioral and functional tests immediately prior to cord blood infusion (baseline) and 6 and 12 months later. Assessment of adverse events across the 12‐month period indicated that the treatment was safe and well tolerated. Significant improvements in children's behavior were observed on parent‐report measures of social communication skills and autism symptoms, clinician ratings of overall autism symptom severity and degree of improvement, standardized measures of expressive vocabulary, and objective eye‐tracking measures of children's attention to social stimuli, indicating that these measures may be useful endpoints in future studies. Behavioral improvements were observed during the first 6 months after infusion and were greater in children with higher baseline nonverbal intelligence quotients. These data will serve as the basis for future studies to determine the efficacy of umbilical cord blood infusions in children with ASD. Stem Cells Translational Medicine 2017;6:1332–1339

Tissue engineering strategies combining molecular targets against inflammation and fibrosis, and umbilical cord blood stem cells to improve hampered muscle and skin regeneration following cleft repair

“…In children with cerebral palsy (motor disorder in childhood), autologous hUCMSCs improved whole brain connectivity and motor function . Similar studies found that infusion of autologous cord blood cells in children with autism spectrum disorder improved behavior and was safe . A 6‐year follow‐up study also demonstrated the long‐term safety profile of hUCMSCs infusion for drug‐resistant systemic lupus erythematosus patients.…”

“…These stem cells can differentiate into the required cell types and secrete regenerative factors . hUCMSCs are save for use in children and adults . while no immunogenic rejection was observed after allogeneic transplantation .…”

Developing Clinically Practicable Biomarkers for Autism Spectrum Disorder

“…Electrophysiological brain recording offers a desirable balance of these characteristics (McPartland 2016), and, though presently less accessible in existing infrastructure, tools such as eye-tracking and wearable autonomic sensors, hold great promise because they can be mass produced at low cost. Indeed, many of these techniques are already being applied in clinical trials (Dawson et al 2017). …”

Immunological Dysfunction in Autism Spectrum Disorder: A Potential Target for Therapy

“…The EyeGaze Tracking showed a 20% increase that the children would gaze at an actress' eyes. Mild adverse events were seen: allergic reactions to infusion, skin changes, agitation, and common childhood infections [115].…”

“…After 2 years, the Pentoxifylline Nausea, vomiting, low blood pressure, and headache [70] Pentoxifylline Limited to the gastrointestinal tract [72] Luteolin Increased irritability [86] Prednisolone Cushing syndrome, irritability. Gastrointestinal bleeding and hypercalcemia (both self-limited) [90] Minocycline Gastrointestinal and upper respiratory symptoms, pica, hematuria, weight gain, hyperactivity, urinary tract infection, otitis media, epistaxis, teeth staining, increased aggression, head-banging, sensitivity to light, appetite loss, and ritualistic behavior [125] Pioglitazone Transitory and self-limited elevations in white blood count, glucose levels, and liver enzymes [133] Oral human immunoglobulin Skin and subcutaneous tissue disorders [103] Oral human immunoglobulin Vomiting, skin rash [103] Intravenous immunoglobulin Mild headaches and infusion-site reactions [108] Mononuclear cells and mesenchymal stem cells Self-limited low-grade fever [110] Autologous cord blood Allergic reaction, skin changes, agitation, and childhood infections [115] Autologous bone marrow-derived mononuclear cells…”