Intrathecal treatment using autologous mesenchymal stem cell neural progenitors (MSC-NP) may improve established disability in MS: results of a phase I open-label trial

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the CNS associated with a progressive clinical course and significant physical disability. There is a critical unmet need to develop therapies that enable repair and neuroprotection. Mesenchymal stem cell-neural progenitors (MSCNPs) are a bone marrow-derived cell population with regenerative potential. Preclinical studies in the EAE mouse model of MS showed that 3 doses of MSCNPs delivered intrathecally (IT) resulted in improved neurological function associated with suppression of local inflammatory response and trophic support for damaged cells at the lesion site. The objective of this FDA-approved phase I clinical trial was to determine safety and tolerability of autologous MSCNPs administered 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. MSCNPs 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 trends in efficacy included a patient-based quality of life assessment, neurological exam, MRI, evoked potentials, and urodynamic testing. All of the 20 enrolled study participants have received autologous IT-MSCNP treatment and the follow up assessments are ongoing. There were no serious adverse events, but minor adverse events such as transient headache or fever occurred in approximately 65% of patients. Improvement in motor function as assessed by patient self-report, neurological examination, or walk speed over 25 feet was seen in 70% of patients. Sustained improvement in disability scores (EDSS) was seen post treatment in the majority of patients. In addition, 60% of patients with bladder dysfunction at baseline demonstrated symptomatic improvement supported by significant increases in urodynamic volumes post-treatment. These interim results indicate that IT MSCNP treatment is safe and well-tolerated, and may reverse established disability as assessed by motor strength and function as well as bladder function in a majority of treated patients. The MSCNP trial is the first of its kind to test IT administration of neural progenitors as a regenerative therapy in MS.

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