Intrathecal Mesenchymal Stem Cell-Neural Progenitor Therapy Shows Therapeutic Response in Subgroups of Progressive MS


In a subgroup of individuals with secondary progressive MS, 50% of patients on mesenchymal stem cell-neural progenitor therapy improved muscle strength compared with 33% of those on placebo.

Morgan Roche, a clinical research assistant at the Tisch MS Research Center of New York

Morgan Roche

Findings from a randomized, double-blind, placebo-controlled trial of patients with progressive multiple sclerosis (MS) suggest that treatment with intrathecal (IT) mesenchymal stem cell-neural progenitor (MSC-NP) may correlate with therapeutic response in a subgroup of individuals.

In a cohort of 54 individuals with either secondary progressive MS (SPMS) or primary progressive MS (PPMS), no significant differences were observed after 1 year of treatment on the primary end point of improvement in either Expanded Disability Status Scale (EDSS), timed 25-foot walk test, or 9-hole peg test (EDSS Plus). Despite this, investigators found differences between groups on 6-minute walk test (6MWT), a secondary end point, when stratified by EDSS, as those with higher scores of 6.0-6.5 showed significantly greater results than placebo.

These data were presented at the 2023 American Academy of Neurology (AAN) Annual Meeting, held April 22-27, in Boston, Massachusetts, by Morgan Roche, a clinical research assistant at the Tisch MS Research Center of New York. The study was a follow-up to a previously completed phase 1 trial (NCT01933802) that showed promising efficacy and safety of IT-MSC-NP treatment in subsets of patients with progressive MS.2

MSC-NPs represent a neural subpoulation of MSCs, characterized by high expression of neural markers including Nestin, down regulation of mesenchymal markers such as smooth muscle a-2 actin and CD90, and reduced multipotency. Of the 54 individuals enrolled, 24 and 27 were randomly assigned to receive 6 IT injections of MSC-NPs or placebo, respectively, every 2 months. In year 2, participants cross over into the opposite group.

Throughout the study, 3 individuals dropped out, and a total of 9 serious adverse events (AEs) were recorded amongst participants, none of which were related to active treatment. Although no differences were seen between groups on the primary outcomes, 50% of patients with SPMS on active therapy demonstrated improvement muscle strength, a secondary outcome, as compared with 33% of those with SPMS on placebo. Additionally, preliminary results from the crossover group in year 2 showed trends in muscle strength and 6MWT after treatment with MSC-NP.1

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Published in Neurology in 2020, the phase 1, open-label, single-arm study included 20 individuals with progressive MS who received 3 IT injections of MSC-NPs 3 months apart, and were followed for 2 years. In total, 18 of the 20 individuals completed the 2-year follow-up protocol, with no long-term AEs observed with repeated IT-MSC-NP treatment. After previously reporting that 8 individuals improved at least 0.5 points on EDSS at 6 months, these improvements were sustained in all but 1 individual at the 2-year time point.2

Additional findings showed that 2 participants demonstrated sustained improvement of 2.0 or greater and 5 individuals sustained EDSS improvement of at least 0.5 points. Three months after treatment, 4 of the 10 ambulatory patients demonstrated at least a 20% improvement in walking speed, and all but 1 of these patients showed a sustained improvement at 2 years. The fourth individual maintained a speed of just below 20% improvement from baseline. Regarding upper-limb function, there were no sustained differences in 9HPT in any of the patients.

Additional biomarkers such as human growth factor (HGF), CXCL12, and IL-8, were significantly increased in cerebrospinal fluid (CSF) post-treatment in nonresponders compared with responders, possibly associating ongoing IT inflammation with lack of response to IT-MSC-NP. While neurofilament light levels appeared to be unchanged after treatment, a handful of patients with elevated CSF NfL greater than 1000 pg/mL who demonstrated a response to IT-MSC-NP showed a decrease in CSF NfL, whereas nonresponders exhibited an increase. None of the candidate biomarkers correlated with age, disease duration or EDSS, with the exception of HGF, which showed a positive correlation with individuals age (P = .018) and disease duration (P = .0004).

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1. Roche M, Malin M, Stark J, Williams A, Harris V, Sadiq S. Efficacy of intrathecal mesenchymal stem cell-neural progenitor therapy in progressive MS: results from a phase 2 clinical trial (S16.005). Presented at: 2023 AAN Annual Meeting; April 22-27; Boston, MA. Abstract 002460
2. Harris VK, Stark JW, Yang S, Zanker S, Tuddenham J, Sadiq SA. Mesenchymal stem cell-derived neural progenitors in progressive MS. Neurol Neuroimmol & Neuroinflamm. 2021;8(1). doi:10.1212/NXI.0000000000000928
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