Intrathecal mesenchymal stem cell-neural progenitor therapy failed to significantly improve the EDSS or the EDSS Plus versus placebo in progressive MS.

Mesenchymal stem cell-neural progenitor therapy (MSC-NPs) are bone marrow-derived cells with trophic and immunomodulatory properties. Their therapeutic potential in MS was evaluated in a randomized, double-blind, placebo-controlled phase 2 trial. Participants had either primary progressive disease (PPMS) or secondary progressive disease (SPMS). They had a significant disability but could still walk (Expanded Disability Status Scale [EDSS], 3.0-6.5). The 51 participants were randomized to six 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, the Timed 25-Foot Walk (T25FW) test, or the 9-hole peg test (9HPT).

There were nine serious adverse events, but none were related to MSC-NP treatment. A total of seven 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 37% of the placebo group. 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 scores of 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 (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 cerebrospinal fluid.

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