Motor function and safety after allogeneic cord blood and cord tissue-derived mesenchymal stromal cells in cerebral palsy: An open-label, randomized trial

Jessica M Sun; Laura E Case; Colleen McLaughlin; Alicia Burgess; Natalie Skergan; Sydney Crane; Joan M Jasien; Mohamad A Mikati; Jesse Troy; Joanne Kurtzberg

doi:10.1111/dmcn.15325

Motor function and safety after allogeneic cord blood and cord tissue-derived mesenchymal stromal cells in cerebral palsy: An open-label, randomized trial

Dev Med Child Neurol. 2022 Dec;64(12):1477-1486. doi: 10.1111/dmcn.15325. Epub 2022 Jul 10.

Authors

Affiliations

¹ Marcus Center for Cellular Cures, Duke University School of Medicine, Durham, NC, USA.
² Department of Physical and Occupational Therapy, Duke University School of Medicine, Durham, NC, USA.
³ Division of Pediatric Neurology, Duke University School of Medicine, Durham, NC, USA.
⁴ Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, USA.

Abstract

Aim: To evaluate safety and motor function after treatment with allogeneic umbilical cord blood (AlloCB) or umbilical cord tissue-derived mesenchymal stromal cells (hCT-MSC) in children with cerebral palsy (CP).

Method: Ninety-one children (52 males, 39 females; median age 3 years 7 months [range 2-5 years]) with CP due to hypoxic-ischemic encephalopathy, stroke, or periventricular leukomalacia were randomized to three arms: (1) the AlloCB group received 10 × 10⁷ AlloCB total nucleated cells (TNC) per kilogram at baseline (n = 31); (2) the hCT-MSC group received 2 × 10⁶ hCT-MSC at baseline, 3 months, and 6 months (n = 28); (3) the natural history control group received 10 × 10⁷ AlloCB TNC per kilogram at 12 months (n = 31). Motor function was assessed with the Gross Motor Function Measure-66 (GMFM-66) and Peabody Developmental Motor Scale, Second Edition.

Results: Infusions (n = 143) were well tolerated, with eight infusion reactions (three in the AlloCB group, five in hCT-MSC) and no other safety concerns. At 12 months, the mean differences (95% confidence intervals [CI]) between actual and expected changes in GMFM-66 score were AlloCB 5.8 points (3.4-8.2), hCT-MSC 4.3 (2.2-6.4), and natural history 3.1 (1.4-5.0). In exploratory, post hoc analysis, the mean GMFM-66 score (95% CI) of the hCT-MSC group was 1.4 points higher than natural history (-1.1 to 4.0; p = 0.27), and the AlloCB group was 3.3 points higher than natural history (0.59-5.93; p = 0.02) after adjustment for baseline Gross Motor Function Classification System level, GMFM-66 score, and etiology.

Interpretation: High-dose AlloCB is a potential cell therapy for CP and should be further tested in a randomized, blinded, placebo-controlled trial.

What this paper adds: Unrelated donor allogeneic umbilical cord blood (AlloCB) and human umbilical cord tissue-derived mesenchymal stromal cell infusion is safe in young children with cerebral palsy. Significant changes in motor function were not observed 6 months after treatment. One year later, treatment with AlloCB was associated with greater increases in Gross Motor Function Measure-66 scores.

Trial registration: ClinicalTrials.gov NCT03473301.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Cell- and Tissue-Based Therapy
Cerebral Palsy* / therapy
Child
Child, Preschool
Female
Fetal Blood
Hematopoietic Stem Cell Transplantation*
Humans
Infant
Male
Mesenchymal Stem Cells*

Associated data

ClinicalTrials.gov/NCT03473301