FDA Approves MSC-NP Therapy as Investigational New Drug in MS Clinical Trial: A Research Milestone

The stem cell research division of the Tisch MS Research Center of New York proudly announces Food and Drug Administration (FDA) approval of autologous, mesenchymal stem cell-derived neural progenitor cells (MSC-NPs) as an Investigational New Drug (IND) for an open label, phase I clinical trial in the treatment of multiple sclerosis. Approximately 20 progressive MS patients, recruited from the existing patient population of the International Multiple Sclerosis Management Practice (IMSMP), will be initially enrolled. The Tisch MS Research Center stem cell trial is the first of its kind in the United States, and incorporates the following key advantages:

• MSC-NPs derived from adult autologous mesenchymal stem cells are the primary therapeutic agent.
• MSC-NPs display a greater potential for differentiation into mature neural tissue, with lower risk for ectopic differentiation.
• MSC-NPs have the capacity for recruitment of existing stem cells within the brain and spinal cord via the induction of immunomodulatory and trophic growth factors.
• MSC-NPs will be administered in multiple rounds of treatment rather than a single treatment.
• Route of administration will be intrathecal (into the cerebrospinal fluid) in order to directly target regenerative mechanisms in the central nervous system.        

 This FDA approval is the culmination of more than a decade of research into the therapeutic potential of stem cells for MS patients and confirmation of the pioneering approach adopted by the Tisch MS stem cell research team led by Saud Sadiq, MD and Violaine Harris, PhD.  The proof-of-concept of this approach was demonstrated in the EAE animal model of MS (Harris et al., J Neurol Sci, 2012). This study showed compelling evidence of the therapeutic potential of intrathecal MSC-NPs in mice with clinically established EAE, which modeled their potential benefit in patients with progressive MS. Pathological findings from the EAE study demonstrated that injected MSC-NPs migrated to areas of demyelination where they seemed to influence the rate of repair through effects on endogenous progenitors in the spinal cord. Furthermore, this study informed the clinical trial design in terms of dosing and dosing frequency. The clinical translation of this stem cell research was further advanced in a publication examining the characteristics of human autologous MSC-NPs from patients with MS (Harris et al., Stem Cells Translational Medicine, 2012). This study showed that bone marrow derived MSC-NPs from MS patients were a feasible source of stem cells for clinical application. Lastly, in an ongoing pilot clinical study, we continue to monitor seven MS patients who received intrathecal autologous MSC-NP infusions between 2005 and 2007 in support of the long-term safety of MSC-NP therapy for MS (Harris et al., manuscript in preparation).

In related stem cell work, we have shown that the immunoregulatory and trophic properties of mesenchymal stem cells may enhance engraftment and remyelinating capability of co-transplanted oligodendrocyte progenitor cells (Cristofanilli et al., Stem Cells and Development, 2011).  More recently, we have explored the capability of the CNS milieu, and specifically cerebrospinal fluid from patients with MS, to support repair through stimulation of an endogenous pool of stem cell (Cristofanilli et al., Neuroscience, 2013).

As important a milestone as the FDA-IND approval is, it marks the true beginning and not the end of our clinical research of stem cell therapy. In this and subsequent studies, we hope to define the optimal therapeutic dose and dosing frequency of stem cells, the best route (or combined routes) of administration, whether or not stem cells should be used in combination with other disease modifying treatments, and which patients are most likely to benefit from this treatment.

The primary objective of the Phase I clinical trial will be to determine safety of autologous MSC-NPs in MS patients who meet inclusion/exclusion criteria after baseline screening. Intrathecal injections of isolated and expanded autologous MSC-NP cells will be performed over a six month period. Study participants will have follow-up visits at multiple timepoints during the treatment phase of the study, and up to 27 months after the final injection. The secondary objective of the trial is to observe trends in efficacy over the course of the three year study.

Enrollment in the clinical trial will commence after approval of the protocol has been obtained from an Institutional Review Board (IRB) and funding has been secured. A definitive date for enrollment to begin will be announced at that time, prior to which no study activities will be conducted. 

UPDATE: February 10, 2015 - Enrollment Completed for Phase I Neural Stem Cell Clinical Trial

The stem cell research division of the Tisch MS Research Center of New York is pleased to announce the completed enrollment of 20 patients to participate in the phase I clinical trial investigating the safety and efficacy of autologous, mesenchymal stem cell-derived neural progenitors (MSC-NPs) for the treatment of multiple sclerosis. We are no longer recruiting for this study. Interim results of this clinical trial will be presented at upcoming scientific conferences and simultaneously announced on our website. All questions regarding participation in any future clinical trials should be discussed with your neurologist. The Tisch MSRCNY is grateful to our patients and benefactors for their ongoing support. 

FDA Approves Stem Cell trial.pdf