Cord Tissue Mesenchymal Stem Cells in the treatment of Autism Spectrum Disorders
Infusion of human umbilical cord tissue mesenchymal stromal cells in children with autism spectrum disorder
Jessica Sun1, Geraldine Dawson2, Lauren Franz2, Jill Howard2, Colleen McLaughlin1, Bethany Kistler1, Barbara Waters-Pick3, Norin Meadows1, Jesse Troy1, Joanne Kurtzberg1
1The Marcus Center for Cellular Cures, Duke University, Durham, North Carolina
2Duke Center for Autism and Brain Development, Duke University, Durham, North Carolina
3Stem Cell Transplant Laboratory, Duke University, Durham, North Carolina
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 manufacturedfrom unrelated donor umbilical cord tissue. Children received one, two, or three doses of 2 × 10(6) 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 ASDspecific 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.
STEM CELLS Transl Med. 2020;1–10. DOI: 10.1002/sctm.19-0434