Phase I Trial of Intrathecal Mesenchymal Stem Cell-derived Neural Progenitors in Progressive Multiple Sclerosis

Violaine K Harris, James Stark, Tamara Vyshkina, Leslie Blackshear, Gloria Joo, Valentina Stefanova, Gabriel Sara, Saud A Sadiq, Violaine K Harris, James Stark, Tamara Vyshkina, Leslie Blackshear, Gloria Joo, Valentina Stefanova, Gabriel Sara, Saud A Sadiq

Abstract

Background: Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system and is one of the leading causes of disability in young adults. Cell therapy is emerging as a therapeutic strategy to promote repair and regeneration in patients with disability associated with progressive MS.

Methods: We conducted a phase I open-label clinical trial investigating the safety and tolerability of autologous bone marrow mesenchymal stem cell-derived neural progenitor (MSC-NP) treatment in 20 patients with progressive MS. MSC-NPs were administered intrathecally (IT) in three separate doses of up to 1 × 107 cells per dose, spaced three months apart. The primary endpoint was to assess safety and tolerability of the treatment. Expanded disability status scale (EDSS), timed 25-ft walk (T25FW), muscle strength, and urodynamic testing were used to evaluate treatment response. This trial is registered with ClinicalTrials.gov, number NCT01933802.

Findings: IT MSC-NP treatment was safe and well tolerated. The 20 enrolled subjects completed all 60 planned treatments without serious adverse effects. Minor adverse events included transient fever and mild headaches usually resolving in <24 h. Post-treatment disability score analysis demonstrated improved median EDSS suggesting possible efficacy. Positive trends were more frequently observed in the subset of SPMS patients and in ambulatory subjects (EDSS ≤ 6.5). In addition, 70% and 50% of the subjects demonstrated improved muscle strength and bladder function, respectively, following IT MSC-NP treatment.

Interpretation: The possible reversal of disability that was observed in a subset of patients warrants a larger phase II placebo-controlled study to establish efficacy of IT MSC-NP treatment in patients with MS.

Funding source: The Damial Foundation.

Keywords: Clinical trial; Intrathecal; Mesenchymal stem cells; Multiple sclerosis.

Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Figures

Fig. 1
Fig. 1
CONSORT flowchart for single-arm, open-label, phase 1 clinical trial of intrathecal autologous MSC-NP in patients with progressive MS.
Fig. 2
Fig. 2
Changes in EDSS score after MSC-NP administration. EDSS scores are depicted for each of the 20 study subjects over the duration of the study (months). IT MSC-NP treatments were initiated at time 0 months. Black bars indicate EDSS scores during the one-year interval prior to receiving the first dose (months −12 to 0). Eight subjects showed ≥0.5 point reduction in EDSS (yellow bars), 10 subjects showed no change in EDSS (blue bars) and 2 subjects showed disease worsening (red bars). Overall, in the 20 study subjects there was a decrease (p = 0.058) in median value from baseline (month 0) EDSS 6.8 to final post-treatment (month 12) EDSS of 6.5 as determined by Wilcoxon Signed-Rank test.

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