Randomized placebo-controlled phase II trial of autologous mesenchymal stem cells in multiple sclerosis

PLoS One. 2014 Dec 1;9(12):e113936. doi: 10.1371/journal.pone.0113936. eCollection 2014.

Abstract

Objective: Uncontrolled studies of mesenchymal stem cells (MSCs) in multiple sclerosis suggested some beneficial effect. In this randomized, double-blind, placebo-controlled, crossover phase II study we investigated their safety and efficacy in relapsing-remitting multiple sclerosis patients. Efficacy was evaluated in terms of cumulative number of gadolinium-enhancing lesions (GEL) on magnetic resonance imaging (MRI) at 6 months and at the end of the study.

Methods: Patients unresponsive to conventional therapy, defined by at least 1 relapse and/or GEL on MRI scan in past 12 months, disease duration 2 to 10 years and Expanded Disability Status Scale (EDSS) 3.0-6.5 were randomized to receive IV 1-2×10(6) bone-marrow-derived-MSCs/Kg or placebo. After 6 months, the treatment was reversed and patients were followed-up for another 6 months. Secondary endpoints were clinical outcomes (relapses and disability by EDSS and MS Functional Composite), and several brain MRI and optical coherence tomography measures. Immunological tests were explored to assess the immunomodulatory effects.

Results: At baseline 9 patients were randomized to receive MSCs (n = 5) or placebo (n = 4). One patient on placebo withdrew after having 3 relapses in the first 5 months. We did not identify any serious adverse events. At 6 months, patients treated with MSCs had a trend to lower mean cumulative number of GEL (3.1, 95% CI = 1.1-8.8 vs 12.3, 95% CI = 4.4-34.5, p = 0.064), and at the end of study to reduced mean GEL (-2.8±5.9 vs 3±5.4, p = 0.075). No significant treatment differences were detected in the secondary endpoints. We observed a non-significant decrease of the frequency of Th1 (CD4+ IFN-γ+) cells in blood of MSCs treated patients.

Conclusion: Bone-marrow-MSCs are safe and may reduce inflammatory MRI parameters supporting their immunomodulatory properties. ClinicalTrials.gov NCT01228266.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • Double-Blind Method
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mesenchymal Stem Cell Transplantation* / adverse effects
  • Mesenchymal Stem Cell Transplantation* / methods
  • Mesenchymal Stem Cells / immunology
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / immunology
  • Multiple Sclerosis, Relapsing-Remitting / pathology
  • Multiple Sclerosis, Relapsing-Remitting / therapy*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology
  • Treatment Outcome
  • Young Adult

Associated data

  • ClinicalTrials.gov/NCT01228266

Grant support

This work was supported by Ministerio de Sanidad y Política Social [grant number TRA-066], Spain. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.