Stem cell therapy improves walking in more advanced progressive MS

Treatment with intrathecal mesenchymal stem cell-neural progenitor therapy (IT-MSC-NP) failed to significantly improve the Expanded Disability Status Scale (EDSS) or the EDSS Plus versus placebo in patients with progressive multiple sclerosis (MS). It may however have a therapeutic effect in a subgroup of MS patients. There was a large placebo effect in this study.

MSC-NPs are bone marrow-derived cells with trophic and immunomodulatory properties. Their therapeutic potential in MS was evaluated in a randomised, double-blind, placebo-controlled phase 2 trial (NCT03355365) [1]. The participants had either primary progressive disease (PPMS) or secondary progressive disease (SPMS). They had a significant disability but could still walk (EDSS 3.0–6.5). The 51 participants were randomised to 6 intrathecal injections of 10 million MSC-NPs (n=24) or saline (n=27) spaced 2 months apart. Due to the compassionate crossover design, participants crossed over into the opposite group in year 2. The primary outcome was EDSS Plus, which means improvement in either EDSS, timed 25-foot walk (T25FW) or 9-hole peg test (9HPT).

There were 9 serious adverse events, but none were related to MSC-NP treatment. A total of 7 participants withdrew from the study. There were no cases of meningitis or malignancies associated with the intervention. Mild headaches and fever were relatively more frequent following MSC-NP treatment. There were no significant differences in the primary endpoint after 1 year. In the MSC-NP group, EDSS Plus improved in 33% of participants, and in the placebo group in 37%. After 2 years, 47 participants received a placebo as well as MSC-NP. In this group, EDSS improved in 20 of 47 patients (43%), 16 patients (34%) remained stable, and 11 (23%) declined.

Regarding secondary endpoints, in patients with EDSS 6.0–6.5, the MSC-NP group performed significantly better than the placebo group on the T25FW (P=0.030), which was confirmed by the 6-minute walk test (6MWT) (P=0.036). In patients with less advanced grey matter (GM) atrophy, GM was relatively better preserved in the treatment group (P=0.021). In addition, in patients with impaired bladder function, 11 of 16 (69%) in the treatment group had improved post-void residual volume versus 4 of 11 (36%) in the placebo group. A biomarker analysis revealed that MDC-NP was associated with increased matrix metalloproteinase 9 and decreased CC chemokine ligands-2 in CSF.

1. 1. Sadiq S. Efficacy of intrathecal mesenchymal stem cell-neural progenitor therapy in progressive MS: Results from a phase II clinical trial. Session S16.005, AAN 2023 Annual Meeting, 22–27 April, Boston, USA.

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