Intrathecal Mesenchymal Stem Cells in Progressive Multiple Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Trial (SMART-MS).
Level 2 - randomized trial
Individual randomized, double-blind, placebo-controlled crossover trial
PubMed 42081777 · doi:10.1212/WNL.0000000000214915
What was done
A randomized, double-blind, placebo-controlled phase I/II crossover trial (SMART-MS) evaluated a single intrathecal injection of autologous bone marrow-derived mesenchymal stem cells (MSCs; 1 × 10⁶ cells/kg) in 18 patients with progressive multiple sclerosis (mean age 46.7 years; 55.6% female) across 4 Norwegian tertiary hospitals. The primary endpoint was the change in combined evoked potential latency at 6 months. Secondary and exploratory outcomes included safety, brain MRI measures, functional and ophthalmologic assessments, serum biomarkers, and CSF proteomics evaluated at 6 and 12 months using baseline-adjusted regression models.
What was found
No significant difference was observed for the primary endpoint of combined evoked potential latency at 6 months (β = -0.31, 95% CI -1.84 to 1.22, p = 0.668). At 6 months, patients in the MSC group showed reduced cerebral atrophy on MRI (β = 9.37, 95% CI 0.29 to 18.45, p = 0.044) and lower serum GFAP levels (β = -16.3 pg/mL, 95% CI -33.0 to 0.3, p = 0.054), but neither effect was sustained at 12 months. Exploratory CSF proteomics showed reductions in multiple inflammation-related proteins at 6 months. One serious adverse event was deemed probably related to MSC treatment. Frequent adverse events after MSC administration included low back pain (n = 10), fever (n = 9), and spinal MRI abnormalities with fluid loculations and nerve root clumping at 6 months (n = 7). One patient developed chronic coccygeal pain attributed to arachnoiditis.
Why it matters
A single intrathecal dose of autologous MSCs provided no electrophysiological evidence of neuroregeneration in progressive MS and caused notable local inflammatory adverse reactions, indicating that intrathecal MSC delivery warrants strong caution.
Limits
The study is limited by a very small sample size (n = 18), which may underpower secondary endpoints. It only evaluated a single administration and short-term follow-up (up to 12 months), and could not assess multi-dose schedules or long-term safety.
Cited by
- contradicts There are no stem cell treatments that have been rigorously tested in controlled, blinded human clinical trials.