Efficacy of Intrathecal Mesenchymal Stem Cell-Neural Progenitor Therapy in Progressive MS: Results from a Phase II Clinical Trial (S16.005)

Abstract

<h3>Objective:</h3> To determine safety and efficacy of intrathecal (IT) mesenchymal stem cell-neural progenitor (MSC-NP) treatment in patients with progressive multiple sclerosis (MS). <h3>Background:</h3> MSC-NPs are bone marrow-derived cells with trophic and immunomodulatory properties with therapeutic potential in MS. In an open-label phase I clinical study in 20 progressive MS subjects, the safety and tolerability of the treatment was demonstrated, and was associated with functional neurological improvement, particularly in ambulatory patients. <h3>Design/Methods:</h3> A phase II randomized, double-blind, placebo-controlled clinical trial was performed to investigate the clinical efficacy of multiple intrathecal (IT) injections of autologous MSC-NPs s associated with clinical efficacy. Study subjects (n=54) were stratified according to EDSS (3.0–6.5) and disease subtype (SPMS/PPMS) and randomized into either treatment or placebo group to receive 6 IT injections of MSC-NPs or placebo every 2 months. In year 2, subjects crossed over into the opposite group. The primary outcome was improvement in either EDSS, timed 25-foot walk or 9-hole peg test (EDSS Plus). Secondary outcomes included 6-minute walk test (6MWT), brain volume, and muscle strength. <h3>Results:</h3> Subjects were randomized into treatment (n=24) or placebo (n=27) groups and 3 subjects dropped out of the study. There were 9 serious adverse events, none of which were related to the study intervention. There were no significant differences in the primary endpoint between the two groups in year 1. In the 6MWT, the placebo group showed significant worsening in distance walked compared to the MSC-NP group, specifically in subjects with higher EDSS (6.0–6.5). Overall, 50% of SPMS subjects in the MSC-NP group demonstrated improved muscle strength compared to 33% of SPMS in the placebo group. Preliminary results from the crossover group in year 2 show similar trends in muscle strength and 6MWT after MSC-NP treatment. <h3>Conclusions:</h3> These results suggest that IT-MSC-NP treatment may correlate with therapeutic response in a subgroup of MS patients. <b>Disclosure:</b> Ms. Roche has nothing to disclose. Miss Malin has nothing to disclose. Dr. Stark has nothing to disclose. Dr. Williams has nothing to disclose. Violaine K. Harris, PhD has nothing to disclose. Dr. Sadiq has nothing to disclose.