Infusion of human umbilical cord tissue mesenchymal stromal cells in children with autism spectrum disorder

• Published in: Stem cells translational medicine 2020-10, Vol.9 (10), p.1137-1146
• Main Authors: Sun, Jessica M., Dawson, Geraldine, Franz, Lauren, Howard, Jill, McLaughlin, Colleen, Kistler, Bethany, Waters‐Pick, Barbara, Meadows, Norin, Troy, Jesse, Kurtzberg, Joanne
• Format: Article
• Language: English
• Subjects: Antibodies; Autism; Autistic children; Behavior; Blood banks; Caregivers; cellular therapy; Children; Clinical trials; Communication; cord tissue; FDA approval; Good Manufacturing Practice; Histocompatibility antigen HLA; Human Clinical; Inflammation; Intravenous administration; Laboratories; Mesenchymal stem cells; mesenchymal stromal cells; Mesenchyme; Stromal cells; Umbilical cord
• ISSN: 2157-6564; 2157-6580
• DOI: 10.1002/sctm.19-0434

Ongoing neuroinflammation may contribute to symptoms of autism spectrum disorder (ASD) in at least a portion of affected individuals. Mesenchymal stromal cells (MSCs) have demonstrated the capacity to modulate neuroinflammation, but safety and feasibility of MSC administration in children with ASD have not been well established. In this open‐label, phase I study, 12 children with ASD between 4 and 9 years of age were treated with intravenous (IV) infusions of human cord tissue mesenchymal stromal cells (hCT‐MSCs), a third‐party MSC product manufactured from unrelated donor umbilical cord tissue. Children received one, two, or three doses of 2 × 106 cells per kilogram at 2‐month intervals. Clinical and laboratory evaluations were performed in person at baseline and 6 months and remotely at 12 months after the final infusion. Aside from agitation during the IV placement and infusion in some participants, hCT‐MSCs were well tolerated. Five participants developed new class I anti‐human leukocyte antigen (HLA) antibodies, associated with a specific lot of hCT‐MSCs or with a partial HLA match between donor and recipient. These antibodies were clinically silent and not associated with any clinical manifestations to date. Six of 12 participants demonstrated improvement in at least two ASD‐specific measures. Manufacturing and administration of hCT‐MSCs appear to be safe and feasible in young children with ASD. Efficacy will be evaluated in a subsequent phase II randomized, placebo‐controlled clinical trial. In this phase I study, intravenous infusion of human cord tissue mesenchymal stromal cell was safe and feasible in young children with autism. Autism symptoms improved in half of children, and 40% developed clinically silent but detectable anti‐human leukocyte antigen antibodies post‐infusion.