Pilot trial of intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis
Jeffrey A Cohen, Peter B Imrey, Sarah M Planchon, Robert A Bermel, Elizabeth Fisher, Robert J Fox, Amit Bar-Or, Susan L Sharp, Thomai T Skaramagas, Patricia Jagodnik, Matt Karafa, Shannon Morrison, Jane Reese Koc, Stanton L Gerson, Hillard M Lazarus, Jeffrey A Cohen, Peter B Imrey, Sarah M Planchon, Robert A Bermel, Elizabeth Fisher, Robert J Fox, Amit Bar-Or, Susan L Sharp, Thomai T Skaramagas, Patricia Jagodnik, Matt Karafa, Shannon Morrison, Jane Reese Koc, Stanton L Gerson, Hillard M Lazarus
Abstract
Background: Mesenchymal stem cells (MSCs) exhibit immunomodulatory, tissue-protective, and repair-promoting properties in vitro and in animals. Clinical trials in several human conditions support the safety and efficacy of MSC transplantation. Published experience in multiple sclerosis (MS) is modest.
Objective: To assess feasibility, safety, and tolerability and explore efficacy of autologous MSC transplantation in MS.
Methods: Participants with relapsing-remitting multiple sclerosis (RRMS) or secondary progressive multiple sclerosis (SPMS), Expanded Disability Status Scale score 3.0-6.5, disease activity or progression in the prior 2 years, and optic nerve involvement were enrolled. Bone-marrow-derived MSCs were culture-expanded and then cryopreserved. After confirming fulfillment of release criteria, 1-2 × 106 MSCs/kg were thawed and administered IV.
Results: In all, 24 of 26 screened patients were infused: 16 women and 8 men, 10 RRMS and 14 SPMS, mean age 46.5, mean Expanded Disability Status Scale score 5.2, 25% with gadolinium-enhancing magnetic resonance imaging (MRI) lesions. Mean cell dosage (requiring 1-3 passages) was 1.9 × 106 MSCs/kg (range, 1.5-2.0) with post-thaw viability uniformly ⩾95%. Cell infusion was tolerated well without treatment-related severe or serious adverse events, or evidence of disease activation.
Conclusion: Autologous MSC transplantation in MS appears feasible, safe, and well tolerated. Future trials to assess efficacy more definitively are warranted.
Trial registration: ClinicalTrials.gov NCT00813969.
Keywords: Multiple sclerosis; clinical trial; disability measures; mesenchymal stem cells; quantitative MRI; safety.
Conflict of interest statement
Declaration of Conflicting Interests
JA Cohen reports consulting fees from Adamas, Merck, Mallinkrodt, Novartis, and Receptos and compensation as Co-Editor of Multiple Sclerosis Journal – Experimental, Translational and Clinical. RA Bermel reports consulting fees from Biogen, Genentech, Genzyme, and Novartis. E Fisher is an employee of Biogen. RJ Fox reports consulting fees from Actelion, Biogen, Genentech, Mallinkrodt, MedDay, Novartis, and Teva and research funding from Novartis. A Bar-OR reports consulting fees from Biogen Merck, Novartis, Receptos, Roche, Sanofi-Genzyme, and Teva. PB Imrey, SM Planchon, SL Sharp, T Skaramagas, P Jogodnik, M Karafa, S Morrison, J Reese Koc, SL Gerson, and HM Lazarus have nothing to disclose.
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Source: PubMed