Background
Mesenchymal stem cells (MSC) have recently garnered the attention of multiple sclerosis (MS) researchers for their remarkable ability to reduce harmful inflammation and promote healing of injured tissue. However, it is not currently known whether MSC can benefit people affected by MS, an autoimmune disease that targets the central nervous system. To date, animal studies in the laboratory and preliminary clinical trials in humans have shown promise that MSC are both safe and potentially effective in reducing inflammation and promoting repair, paving the road for larger, more comprehensive studies to investigate the therapeutic benefits of MSC treatment in people with MS.
The discovered potential of MSC in treating MS has culminated in the launch of MESCAMS (MEsenchymal Stem cell therapy for CAnadian MS patients), a phase II clinical trial that is funded in part by the MS Scientific Research Foundation, Research Manitoba, and A&W Food Services of Canada Inc. Spearheaded by Dr. Mark Freedman (Ottawa Hospital Research Institute, University of Ottawa), principal investigator (PI) at the Ottawa site and Dr. James Marriott (University of Manitoba), PI at the Manitoba site, MESCAMS is part of an international mesenchymal stem cell research effort encompassing nine countries.
The aim of this study is to determine if treatment with autologous (originating from the same person receiving treatment) MSC in people with MS is safe, can reduce harmful inflammation in the brain, and possibly contribute to repair of the central nervous system.
The Study
The MESCAMS study is a randomized, double-blind, cross-over study involving 40 patients across two sites: The Ottawa Hospital and Health Sciences Centre (HSC) Winnipeg. The trial will include participants affected by relapsing-remitting MS in whom existing therapies have not worked optimally, as well as select individuals with secondary and primary progressive forms of MS. Participants will be randomly assigned to one of two treatment groups, but all participants will be injected intravenously (IV) with MSC collected from their own bone marrow at some point in the study, depending on their group:
- Early treatment group: participants are given a single infusion of autologous MSC at week 0, then cross over at week 24 to receive a placebo infusion.
- Late treatment group: participants are given a single placebo infusion at week 0, then cross over at week 24 to receive an infusion of autologous MSC.
All participants will be followed for 48 weeks. Over the course of the study, the participants will be assessed to determine the safety of autologous MSC by checking for side effects and documenting these adverse health events. In addition, the researchers will examine any potential clinical benefits of MSC therapy, including reduction of inflammatory injury in the brain as measured by magnetic resonance imaging (MRI), number of relapses, disability progression, and several potential indicators of repair in the central nervous system.
Comment
The MESCAMS study is the first Canadian clinical trial evaluating the safety and efficacy of MSC as a treatment for multiple sclerosis. This marks an important step forward in MS research and treatment, as early experiments with stem cell therapies have shown encouraging results. One major factor which distinguishes this study from the previously conducted Canadian bone marrow transplantation (BMT) trial is that participants are not subjected to intensive chemotherapy, which is required prior to BMT to effectively eliminate the diseased immune system.
MSC therapy, on the other hand, works by subduing the harmful immune cells that drive MS, and so the researchers anticipate that the procedure will carry a lower risk to participants, since no chemotherapy is required and the MSC have the potential of controlling inflammation in the absence of other MS medications. As well, the study design uses autologous MSC, in which each participant receives their own stem cells, thus diminishing the risk of the participant’s immune system rejecting the cells.
The results of the MESCAMS trial will be pooled with data emerging from the concurrent international MSC trial, culminating in a rich body of information that could not otherwise be attained by individual research centres alone. The Canadian contribution to the trial is poised to make Canada a leader in researching MSC therapy in MS, largely owing to the seasoned expertise of the lead investigators and other collaborators, as well as substantial investment into state-of-the-art stem cell facilities built in compliance with stringent government regulations. Ultimately, the hope is that the findings from the MESCAMS study will build on results seen in pioneering MSC studies and help lead to treatment options for people with MS.