Promising results of intrathecal MSC-NTF cells in progressive MS

Intrathecal administration of MSC-NTF cells showed a favourable safety profile in patients with progressive MS. Further post-treatment cerebrospinal fluid (CSF) analysis demonstrated a reduction in neuroinflammatory biomarkers and an increase in neuroprotective biomarkers. Additional exploratory analyses showed improvements in clinical outcome measures following intrathecal MSC-NTF cell therapy [1].

The pathogenesis of progressive MS includes CNS inflammation, chronic demyelination, and neurodegeneration [2]. The current open-label, phase 2, BCT-101 trial (NCT03799718) aimed to investigate the safety and efficacy of MSC-NTF cells –autologous bone-marrow-derived mesenchymal stem cells, induced in culture to secrete higher levels of neuroprotective factors– in a population of patients with progressive MS. Administration of intrathecal MSC-NTF cells (dosing 100–125 x 10⁶) was performed 3 times, with 8-week intervals, in 18 patients (primary progressive MS, n=4; secondary progressive MS, n=14). Safety was the primary outcome at week 28. Secondary outcome measures included neurological biomarkers and clinical outcome measures. The findings were presented by Dr Jeffrey A. Cohen (Cleveland Clinic, OH, USA).

Headache (88.9%) and back pain (83.3%) were the most common adverse events (AEs). Dr Cohen added that most headaches were related to the lumbar punction, which was the method of therapy administration. Other common AEs were urinary tract infections (33.3%), musculoskeletal pain (27.8%), and injection site pain (22.2%). Two patients had serious AEs of arachnoiditis, one of whom discontinued the study. Regarding the efficacy of intrathecal MSC-NTF cells, CSF neuroinflammatory biomarkers displayed a trend towards reduction (VEGF, HGF), whereas CSF biomarkers of neuroprotection showed a trend of increase (MCP-1, SDF-1 and Osteopontin).

In addition, patients of the current trial were matched to patients of the CLIMB registry (n=48) and the SPRINT-MS trial (NCT01982942) (n=244). Comparing the number of patients with ≥25% improvement on the 9-Hole Peg Test (9-HPT), MSC-NTF receivers (13%) showed numerical benefits over patients from the CLIMB registry (0%), and ibudilast receivers (2%) and placebo receivers (3%) of the SPRINT-MS trial. Similarly, 2.5% Low-Contrast Letter Acuity Chart (LCLA) (≥8 letter improvement) favoured receivers of MSC-NTF cells (27%) over patients of the CLIMB registry (6%), and SPRINT-MS trial (16%, 13%). Finally, a numerically higher proportion of patients achieved ≥5 point improvement on the Symbol Digit Modalities Test (SDMT) when receiving MSC-NTF cells (47%) compared with patients of the CLIMB registry (2%) and patients of the SPRINT-MS trial (27%, 26%).

Due to the open-label, uncontrolled design of the study, clinical outcome measures need to be interpreted with caution. The results of the clinical outcome measures were largely reported descriptively, and no formal statistical analyses were performed. Therefore, a randomised, placebo-controlled trial should be conducted to confirm the results of this study. Dr Cohen mentioned that similar effects were observed for patients with primary progressive MS and patients with secondary progressive MS. However, solid conclusions on this aspect of the study cannot be made, due to the limited sample size.

1. Cohen J, et al. Multicenter Phase 2 Safety and Efficacy Study of MSC-NTF Cells (NurOwn) in Progressive Multiple Sclerosis. OP114, ECTRIMS 2021 Virtual Congress, 13–15 October.
2. Baecher-Allan C, et al. 2018;97(4):742-768.

 

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Posted on 9 December 202115 February 2024