To evaluate therapeutic efficacy of repeated dosing of intrathecal mesenchymal stem cell-derived neural progenitor (IT-MSC-NP) treatment in patients with progressive MS.

MSC-NPs are an autologous bone marrow-derived population of cells currently under investigation as a novel MS treatment targeting CNS repair. Preclinical evidence suggests that MSC-NPs function through immunoregulatory/trophic mechanisms. The open-label phase I clinical trial in 20 patients with progressive MS demonstrated safety and tolerability of the treatment, and was associated with functional neurological improvement, particularly in ambulatory patients. Whether or not these improvements are sustained and quantifiable against a placebo control remains unknown.

Bone marrow MSCs were isolated, expanded, and cultured with neural progenitor media to generate MSC-NPs. In the phase I trial, IT-MSC-NPs were injected with 3 doses of up to 10 million cells every 3 months with follow-up EDSS assessments performed 12 and 30 months following the start of the treatment. The phase II trial is a double-blind, placebo-controlled, randomized crossover study in 50 patients with progressive MS, consisting of 6 doses of IT-MSC-NPs every 2 months.

Eight of the 20 subjects in the phase I trial showed EDSS improvements (range 0.5 to 3.5 point improvement) after 12 months. The 30 month follow-up in 18 out of 20 subjects demonstrated that 7 subjects (39%) showed continued sustained improvement in EDSS. One subject who had previously demonstrated 1.0 improvement, demonstrated slight worsening in year 2. In the remaining subjects, 33% had continued stable EDSS, and 22% showed continued disease progression. These results suggest that additional treatments may be required to sustain the full effect of IT-MSC-NP treatment. A phase II trial is underway to investigate the safety and efficacy of 6 separate IT-MSC-NP treatments compared to a placebo IT-saline control.

IT-MSC-NP therapy is a promising regenerative therapy for progressive MS.