Phase I Trial of Intrathecal Mesenchymal Stem Cell-derived Neural Progenitors in Progressive Multiple Sclerosis

• Published in: EBioMedicine Vol. 29; pp. 23 - 30
• Main Authors: Harris, Violaine K., Stark, James, Vyshkina, Tamara, Blackshear, Leslie, Joo, Gloria, Stefanova, Valentina, Sara, Gabriel, Sadiq, Saud A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2018; Elsevier
• Subjects: Adult; Advanced Basic Science; Aged; Biomarkers; Cell Differentiation; Cell- and Tissue-Based Therapy - methods; Clinical trial; Female; Humans; Injections, Spinal; Internal Medicine; Intrathecal; Magnetic Resonance Imaging; Male; Mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Middle Aged; Multiple sclerosis; Multiple Sclerosis - diagnosis; Multiple Sclerosis - immunology; Multiple Sclerosis - metabolism; Multiple Sclerosis - therapy; Neural Stem Cells - cytology; Neural Stem Cells - metabolism; Research Paper; Stem Cell Transplantation - adverse effects; Stem Cell Transplantation - methods; Symptom Assessment; Time Factors; Transplantation, Autologous; Treatment Outcome; Clinical trial; Multiple sclerosis; Intrathecal; Mesenchymal stem cells
• ISSN: 2352-3964; 2352-3964
• DOI: 10.1016/j.ebiom.2018.02.002

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system and is one of the leading causes of disability in young adults. Cell therapy is emerging as a therapeutic strategy to promote repair and regeneration in patients with disability associated with progressive MS. We conducted a phase I open-label clinical trial investigating the safety and tolerability of autologous bone marrow mesenchymal stem cell-derived neural progenitor (MSC-NP) treatment in 20 patients with progressive MS. MSC-NPs were administered intrathecally (IT) in three separate doses of up to 1 × 107 cells per dose, spaced three months apart. The primary endpoint was to assess safety and tolerability of the treatment. Expanded disability status scale (EDSS), timed 25-ft walk (T25FW), muscle strength, and urodynamic testing were used to evaluate treatment response. This trial is registered with ClinicalTrials.gov, number NCT01933802. IT MSC-NP treatment was safe and well tolerated. The 20 enrolled subjects completed all 60 planned treatments without serious adverse effects. Minor adverse events included transient fever and mild headaches usually resolving in <24 h. Post-treatment disability score analysis demonstrated improved median EDSS suggesting possible efficacy. Positive trends were more frequently observed in the subset of SPMS patients and in ambulatory subjects (EDSS ≤ 6.5). In addition, 70% and 50% of the subjects demonstrated improved muscle strength and bladder function, respectively, following IT MSC-NP treatment. The possible reversal of disability that was observed in a subset of patients warrants a larger phase II placebo-controlled study to establish efficacy of IT MSC-NP treatment in patients with MS. The Damial Foundation. •In this phase I study repeated intrathecal dosing of autologous MSC-NPs in patients with progressive MS was well tolerated.•Dose of up to 10 million cells was safe and not associated with any significant adverse events.•The treatment was associated with functional neurological improvement, particularly in ambulatory patients. Multiple sclerosis is one of the leading causes of disability in young adults. Our study is the first evidence suggesting that a cell-based therapeutic approach is capable of reversing disability in multiple sclerosis. Results of our study add to existing evidence demonstrating the safety and tolerability of intrathecal administration of autologous mesenchymal stem cell-derived neural progenitors. Our study was uniquely associated with repeated administrations of cells freshly harvested from culture, as opposed to cryopreserved cells thawed at the bedside, which may have contributed to the observed efficacy of the treatment. The continued development of this therapeutic approach will likely have implications for treating other neurological diseases.