Phase I Clinical Trial Demonstrates Safety and Efficacy of Repeated Intrathecal Mesenchymal Stem Cell-Derived Neural Progenitors in Progressive Multiple Sclerosis

Multiple sclerosis (MS) is a chronic autoimmune disease with disseminated inflammatory CNS demyelination and axonal damage. In many patients, MS becomes progressive over time, leading to an accumulation of irreversible disability. Therapies aimed at preventing or slowing progressive MS by enabling repair and neuroprotection are still lacking. We have investigated a neural progenitor-like subpopulation of mesenchymal stem cells (MSC-NPs) that exhibit immunoregulatory and trophic properties both in vitro and in vivo. The objective of this FDA-approved phase I, open label clinical trial was to determine safety and tolerability of autologous MSC-NPs administered intrathecally (IT) in 3 doses of up to 10 million cells per injection, spaced 3 months apart. Twenty MS patients with established disability and relatively stable disease were enrolled. MSC-NPs expanded from autologous bone marrow were batch-tested for quality, sterility, and chromosomal stability. Primary safety outcomes included adverse event assessments. Secondary outcomes to observe efficacy included change in muscle strength (MRC), EDSS (expanded disability status score), timed 25 foot walk (T25FW), and urodynamics testing for bladder function. Repeated dosing of MSC-NPs was safe and well tolerated, with only minor adverse events including transient headache and fever. Of the 20 study subjects, 15 (or 75%) demonstrated functional neurological improvement associated with IT-MSC-NP treatment. These positive trends in efficacy demonstrate functional neurological improvement within a group of MS patients who had otherwise stable disability for a year prior to the study. Improvements were more frequently observed in subjects who were ambulatory (EDSS ≤ 6.5) upon enrolling in the study. The encouraging safety and efficacy results from the phase I trial warrant a larger phase II placebo-controlled study to confirm efficacy of intrathecal MSC-NP treatment in patients with MS.

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