Results of this trial suggest that when adequately dosed, an intravenous infusion of autologous umbilical cord blood improves whole brain connectivity and motor function in young children with cerebral palsy.

 

Authors
Jessica M. Sun, Allen W. Song, Laura E. Case, Mohamad A. Mikati, Kathryn E. Gustafson, Ryan Simmons, Ricki Goldstein, Jodi Petry, Colleen McLaughlin, Barbara Waters-Pick, Lyon W. Chen, Stephen Wease, Beth Blackwell, Gordon Worley, Jesse Troy, Joanne Kurtzberg

 

First published: 28 October 2017
Authored by a member of CBA

 

Abstract

 

Cerebral palsy (CP) is a condition affecting young children that causes lifelong disabilities. Umbilical cord blood cells improve motor function in experimental systems via paracrine signaling. After demonstrating safety, we conducted a Phase II trial of autologous cord blood (ACB) infusion in children with CP to test whether ACB could improve function (ClinicalTrials.gov, NCT01147653; IND 14360). In this double-blind, placebo-controlled, crossover study of a single intravenous infusion of 1–5 × 107 total nucleated cells per kilogram of ACB, children ages 1 to 6 years with CP were randomly assigned to receive ACB or placebo at baseline, followed by the alternate infusion 1 year later. Motor function and magnetic resonance imaging brain connectivity studies were performed at baseline, 1, and 2 years post-treatment. The primary endpoint was change in motor function 1 year after baseline infusion. Additional analyses were performed at 2 years. Sixty-three children (median age 2.1 years) were randomized to treatment (n = 32) or placebo (n = 31) at baseline. Although there was no difference in mean change in Gross Motor Function Measure-66 (GMFM-66) scores at 1 year between placebo and treated groups, a dosing effect was identified. In an analysis 1 year post-ACB treatment, those who received doses ≥2 × 107/kg demonstrated significantly greater increases in GMFM-66 scores above those predicted by age and severity, as well as in Peabody Developmental Motor Scales-2 Gross Motor Quotient scores and normalized brain connectivity. Results of this study suggest that appropriately dosed ACB infusion improves brain connectivity and gross motor function in young children with CP.

STEM CELLS TRANSLATIONAL MEDICINE 2017

 

Significance Statement

 

Results of this trial suggest that when adequately dosed, an intravenous infusion of autologous umbilical cord blood improves whole brain connectivity and motor function in young children with cerebral palsy.

 

Introduction

 

Cerebral palsy (CP), the most prevalent motor disorder of childhood, affects two to three per 1,000 live births [1]. CP typically results from in utero or perinatal brain injury such as hypoxic insult, hemorrhage, or stroke. Affected children have varying degrees of functional impairments from mild limitations in advanced motor skills to severely limited self-mobility despite use of assistive technology resulting in a lifelong inability to function independently. Currently, the cornerstone of treatment is various therapies to optimize function and quality of life. However, no curative therapies are available.
Improved motor function has been demonstrated in animal models of ischemic brain injury and CP after administration of human umbilical cord blood cells [2, 3]. Evidence suggests that cord blood cells act via paracrine signaling endogenous cells to facilitate repair. This led us to hypothesize that intravenous (IV) infusion of autologous cord blood (ACB) would improve motor function in young children with CP. After demonstration of safety in 184 children [4], we conducted a randomized, placebo-controlled trial testing the efficacy of a single IV ACB infusion in young children with CP.

 

Materials and Methods

 

Study Design
We conducted a single-center, Phase II, prospective, randomized, double-blind, placebo-controlled, crossover study of a single IV ACB infusion in children ages 1 to 6 years with CP (Fig. 1) at Duke University. The study was approved by the Duke Institutional Review Board and conducted under FDA IND14360.

 

Original Article

 

LFLN REF:02112017.p.91