Stem cell therapy fails primary endpoint but improves walking in more advanced progressive MS

Treatment with intrathecal mesenchymal stem cell-derived neural progenitor (MSC-NP) therapy failed to significantly improve the Expanded Disability Status Scale (EDSS) or the EDSS Plus compared with placebo in patients with progressive multiple sclerosis (MS). However, MSC-NP may have a therapeutic effect in a subgroup of patients. A large placebo effect was observed 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]. Participants had either primary progressive disease (PPMS) or secondary progressive disease (SPMS) and 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. The compassionate crossover design allowed participants to change to the opposite group in year 2. The primary outcome was EDSS Plus, which means improved EDSS, timed 25-foot walk (T25FW), or 9-hole peg test (9HPT).

After 1 year, no significant differences were seen in the primary endpoint. 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 participants (43%), 16 participants (34%) remained stable, and 11 (23%) declined.

There were no serious adverse events related to MSC-NP treatment. A total of 7 participants withdrew from the study and no cases of meningitis or malignancies associated with the intervention were observed. Mild headaches and fever were relatively more frequent following MSC-NP treatment.

Regarding secondary endpoints, in participants with EDSS 6.0–6.5, the MSC-NP group performed significantly better than the placebo group on the T25FW (P=0.030), confirmed by the 6-minute walk test (P=0.036). In participants with less advanced grey matter atrophy, grey matter was better preserved in the treatment group (P=0.021). Furthermore, of participants 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 MSC-NP was associated with increased matrix metalloproteinase 9 and decreased CC chemokine ligand-2 in the cerebrospinal fluid.

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

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Posted on 26 June 202325 March 2024