Multiple Intrathecal Dosing of Neural Progenitors Administered to Progressive MS Patients with Disability Is Safe and Improves Disability Scores (I10.008)

OBJECTIVE: To evaluate safety, tolerability, and preliminary efficacy of three intrathecal (IT) administrations of autologous mesenchymal stem cell-derived neural progenitors (MSC-NPs) in progressive multiple sclerosis (MS). BACKGROUND: MSC-NPs are an autologous bone marrow-derived population with regenerative potential. Preclinical studies in mouse EAE resulted in improved neurological function, suppression of local inflammatory response, and trophic support at the lesion site. Pilot clinical experience with IT MSC-NPs in six MS patients also supported the dosing, safety, and potential efficacy of this therapy. DESIGN/METHODS: The study is an FDA-approved phase I clinical trial of autologous MSC-NPs administered IT in three doses of up to 10 million cells per injection, spaced three months apart. Enrollment includes 20 MS patients with established disability (range 3.5 to 8.5) and relatively stable disease as evidenced by less than 1.0 point change in EDSS in the last year, and stable MRI disease burden with no enhancing lesions in the last six months. Primary safety outcomes include adverse event assessments. Secondary efficacy outcomes include EDSS, timed 25 foot walk, PEG test, PASAT, evoked potentials, and urodynamics testing. Patients are followed 3 months and 6 months after treatment. RESULTS: IT-MSC-NPs have been administered to all 20 study participants. Thirteen out of 20 have received all 3 doses and 3-month follow up. There were no serious adverse events, and minor adverse events included transient headache and/or fever in approximately 65[percnt] of patients. Neurological improvements were observed in a subset of patients after treatment, which included improved EDSS, improved PEG tests, and better bladder function clinically and on urodynamic testing. CONCLUSIONS: The MSC-NP trial is the first of its kind to test IT administration of neural progenitors as a regenerative MS therapy and appears safe and well tolerated. Based on the promising efficacy trends, a phase II trial is warranted. Disclosure: Dr. Sadiq has nothing to disclose. Dr. Blackshear has nothing to disclose. Dr. Joo has nothing to disclose. Dr. Vyshkina has nothing to disclose. Dr. Harris has nothing to disclose.