Phase I Clinical Trial Demonstrates Safety and Efficacy of Intrathecal Autologous Mesenchymal Stem Cell-Derived Neural Progenitors (MSC-NPs) for the Treatment of Progressive Multiple Sclerosis

OBJECTIVE: To establish safety and tolerability, and to evaluate efficacy of repeated intrathecal (IT) administration of MSC-NPs in progressive MS.

BACKGROUND: There is a need to develop therapies that restore neurological function in progressive multiple sclerosis (MS) patients with disability. Mesenchymal stem cell-neural progenitors (MSC-NPs) are autologous bone marrow-derived cells with regenerative potential based on their release of trophic and immunomodulatory factors. Multiple IT doses of MSC-NPs were shown to improve neurological function in EAE mice.

METHODS: The study is an FDA-approved phase I clinical trial of autologous MSC-NPs administered in three IT doses of 10 million cells, spaced three months apart. Enrollment included 20 progressive MS patients with established disability (EDSS 3.5 to 8.5) and stabilized disease as evidenced by <1.0 point change in EDSS in the last year, and stable MRI disease burden with no enhancing lesions in the last six months. Outcome assessments included adverse event reporting, EDSS, timed 25 foot walk (T25FW), 9-hole peg test (9HPT), and urodynamics testing. Patients were followed 3 and 6 months after treatment.

RESULTS: Twenty study participants received 3 treatments of IT-MSC-NPs. No serious adverse events were observed. Transient headache and fever were observed in 72% and 15% of treatments, respectively. Neurological improvements were observed in the majority of patients. Remarkably, 15 out of 20 subjects demonstrated increased individual muscle strength as determined by MRC, and 8 out of 20 subjects demonstrated improved EDSS of ≥0.5 points after treatment. Only 2 subjects showed continued disease worsening. Improvements were also noted in T25FW and 9HPT. Urodynamics testing demonstrated bladder function improvement in 35% of subjects after treatment.

CONCLUSIONS: The study is the first of its kind to test IT-MSC-NP as a regenerative MS therapy. Positive safety and efficacy data has led to the initiation of a phase II, double blind, placebo-controlled trial.