The Tisch MS Research Center of New York is delighted to announce the commencement of the first ever clinical trial of neural progenitor cells derived from bone marrow stem cells in the treatment of multiple sclerosis, entitled “Autologous, Bone Marrow-Derived Mesenchymal Stem Cell-Derived Neural Progenitor Cells, Expanded Ex Vivo; Administered Intrathecally.” This study was recently IRB-approved by the International Cellular Medicine Society and patient recruitment will begin in January 2012.
In this open label safety and tolerability study, 20 participants with a confirmed diagnosis of progressive MS will be recruited from the affiliated International Multiple Sclerosis Management Practice. Participants will undergo bone marrow aspiration, from which mesenchymal stem cells (MSCs) will be isolated and expanded ex vivo. Following bone marrow collection neural progenitor cells (MSC-NPs) derived from these MSCs will be selected, cultured, and subjected to testing for identity, purity, and sterility. Intrathecal injections of autologous MSC-NPs will begin three months after their initial enrollment, with two further rounds of injections to follow at three month intervals. Follow up visits will continue for 27 months following the final injection round, bringing the total duration of participation to three years.
Our objectives in conducting this study are to determine the safety of using autologous MSC-NP therapies in MS, the tolerability of intrathecal injection as an administration route, and the efficacy of this approach for promoting remyelination and neuronal repair in cases of progressive MS with significant disability over the three year duration of the study. As this is the first clinical study testing intrathecal MSC-NP therapy in MS, the expected outcomes are necessarily uncertain. However, the clinical safety of this approach is supported by pilot studies conducted in Israel,1Lebanon,2and Iran3which showed that intrathecal MSC injection is a safe and viable treatment option for patients with MS.
MSC-NPs were preferentially chosen for this study because they exhibit a number of properties that support their therapeutic potential in the central nervous system (CNS) including; (1) MSC-NPs are neuroectodermally committed and may be more suitable for administration directly into the CNS; (2) MSC-NPs have reduced capacity for multipotential differentiation thus reducing potential risk of ectopic tissue formation in the CNS; and (3) MSC-NPs have immunomodulatory and trophic properties hypothesized to promote repair duing CNS damage.4Preclinical studies in the EAE animal model conducted at Tisch MS have shown that multiple intrathecal injections of MSC-NPs were much more effective at reducing disability in mice with EAE than single injections.5Furthermore, intrathecal injections of MSC-NPs initiated during the chronic phase of EAE in mice demonstrated significant neurological improvement associated with increased myelination.5
This clinical trial is the culmination of years of research at Tisch MS supervised by Violaine Harris, Ph.D and Saud Sadiq, MD. A selection of previously published research for which abstracts are available online includes "Human Mesenchymal Stem Cell-Derived Neural Progenitors (MSC-NPs) Exhibit Trophic Properties that May Influence Repair in MS," "Use of Autologous Mesenchymal Stem Cells for Neural Repair," and "Mesenchymal Stem Cells Enhance the Engraftment and Myelinating Ability of Allogeneic Oligodendrocyte Progenitors in Dysmyelinated Mice."
1. Karussis D, Karageorgiou C, Vaknin-Dembinsky A, et al. Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol. 2010 Oct;67(10):1187-94.
2. Yamout B, Hourani R, Salti H, et al. Bone marrow mesenchymal stem cell transplantation in patients with multiple sclerosis: a pilot study. J Neuroimmunol. 2010 Oct 8;227(1-2):185-9.
3. Mohyeddin Bonab M, Yazdanbakhsh S, Lotfi J, et al. Does mesenchymal stem cell therapy help multiple sclerosis patients? Report of a pilot study. Iran J Immunol. 2007 Mar;4(1):50-7.
4. Harris VK, Faroqui R, Vyshkina T, Sadiq SA. Characterization of autologous neural progenitors for use in multiple sclerosis. manuscript submitted. 2011.
5. Harris VK, Yan QJ, Vyshkina T, Sahabi S, Liu X, Sadiq SA. Clinical and pathological effects of intrathecal injection of mesenchymal stem cell-derived neural progenitors in an experimental model of multiple sclerosis. J Neurol Sci. 313: 167-177, 2012.