Protocol for a Pilot Phase IIa Randomized, Placebo-Controlled, Double-Blind, Crossover Study of Umbilical Cord-Derived Mesenchymal Stem Cells (UCMSC) for the Treatment of Relapsing-Remitting Multiple Sclerosis (RRMS):The MSCell Study

Abstract

Introduction: Multiple sclerosis (MS) is a chronic autoimmune, demyelinating, and neurodegenerative disease of the central nervous system, the relapsing-remitting (RRMS) form affects around 85% of patients at the beginning. While current disease-modifying therapies (DMTs) reduce relapses and slow disability progression, they have significant side effects and do not promote neural repair. Umbilical cord-derived mesenchymal stem cells (UCMSC) offer potential for immunomodulation, neuroprotection, and repair in MS without the intensive immunoablation required for autologous hematopoietic stem cell transplantation (AHSCT).

Methods: This single center, randomized, double-blind, crossover phase IIa trial will evaluate the safety and feasibility of intravenous UCMSC administration in active RRMS patients. Participants will receive either UCMSC or placebo in a 1:1 ratio, with a crossover to the alternate treatment after 24 weeks. Primary outcomes include safety, measured by adverse events, and feasibility, assessed through recruitment, retention, and dropout rates. Secondary outcomes involve clinical and paraclinical indicators, including disability, quality of life, fatigue, mood disorders, and inflammation markers.

Discussion: This trial aims to address the safety and feasibility of UCMSCs in RRMS. If both aspects are corroborated, and a trend of efficacy is noted in the exploratory outcomes, then a larger study is warranted to further explore this therapeutic option with fewer side effects and potential for enhanced neuroprotection and repair. Successful results may also lead to broader applications in other autoimmune and neurodegenerative diseases, fostering interdisciplinary collaboration and advancing MS research and treatment.

Conclusion: This exploratory phase IIa study will provide valuable insights into the safety and feasibility of UCMSC in treating RRMS, highlighting the need for further research to optimize dosing and administration routes, and confirming efficacy in larger, more diverse populations.