MESCAMS: A recap and what’s next?

On January 29, I was pleased to be part of an exciting announcement made by the MS Society to fund a $4.2 million grant for MESCAMS (MEsenchymal Stem cell therapy for CAnadian MS patients), the Canadian arm of an international study that’s probing the safety and efficacy of treatment with mesenchymal stem cells for MS.

The bright and airy Courtyard Café at Winnipeg Health Sciences Centre was packed with special guests and enthusiastic media to witness the announcement of this landmark clinical trial, a collaborative effort led by two eminent Canadian researchers and stem cell experts – Dr. Mark Freedman at Ottawa Hospital Research Institute, University of Ottawa, and Dr. James Marriott at University of Manitoba – and jointly funded by the MS Society, MS Scientific Research Foundation, Research Manitoba, and A&W Food Services of Canada Inc.

Both conventional and social media were ablaze with updates as Mr. Yves Savoie, President and CEO of the MS Society, unveiled the study and lauded prospective participants as “pioneers in [the pursuit of] research breakthroughs” that will unlock new answers for people living with MS. One of those individuals living with MS, Ms. Lizelle Mendoza – who was diagnosed in 2007 – took to the podium and deeply moved us with her words of optimism, saying that she was “overjoyed and filled with hope” when she learned about the new trial for stem cell therapy. To Lizelle and other Canadians living with MS, this study marks an important step forward in unraveling the mystery of MS and developing new and effective treatments for this unpredictable disease.

 

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Ms. Lizelle Mendoza, Dr. James Marriott and I at the MESCAMS announcement.

The subject of stem cells is steeped in ethical discussion, and can provoke questions and, in some cases, strong reactions from the public. I hear a lot of questions about stem cell therapy, such as “what is the source of stem cells used in MS research?” and, “what are the risks and benefits of stem cell therapy?” In this post, I will explain mesenchymal stem cells and the MESCAMS study in particular, in the hopes of clarifying any misconceptions surrounding this promising therapy.

What are mesenchymal stem cells?

Stem cells are a special class of cells that have two important properties. The first is the ability to produce exact copies of themselves, through a process called self-renewal. The second is to transform and mature into specialized cell types with certain functions (for example, a blood cell or a nerve cell).

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 Fluorescence microscopy photo of a mesenchymal stem cell (Image credits: EuroStemCell.org)

Stem cells are the engines of the body that give rise to tissues and organs, as well as maintain and repair certain tissues when they become damaged. Stem cells can be divided into different categories depending on their potential for transforming (or differentiating) into a diverse range of cell types. Embryonic stem cells, which as the name suggests are derived from an embryo, can differentiate into nearly any kind of cell type and are the building blocks for the entire body during development. Embryonic stem cells only exist in the developing embryo for a short period of time, which makes it difficult to access these stem cells. The more specialized adult stem cells (a category to which mesenchymal stem cells belong), on the other hand, are more limited in the types of cells they can differentiate into, and are generally involved in repairing damaged tissues or replacing aging cells. Adult stem cells exist in many adult tissues and although some go on to develop into tissues, others stay as stem cells which makes them easier to extract from the body. The source of stem cells for therapeutic purposes can vary. Some treatments are autologous, meaning the stem cells are harvested from the individual that is being treated. Other treatments are allogeneic, meaning the stem cells are from a donor.

Mesenchymal stem cells are a type of adult stem cell found predominantly in the bone marrow, but have also been reported to reside in muscle, fat, and umbilical cord blood. These stem cells can give rise to certain tissues of the body, including cells making up cartilage, bone and fat. Although mesenchymal stem cells have traditionally been investigated by researchers for their regenerative potential for bone and cartilage injuries, they also hold promise for people living with MS due to their capacity to suppress inflammation and assist in the repair of damaged nervous tissue. Studies exploring the therapeutic benefits of mesenchymal stem cell therapies for MS are in their infancy, but the results to date have been so encouraging so as to warrant a concerted, international effort in the scientific community to accelerate research into testing the safety and feasibility of this therapy in people living with MS.

Take a look at our MS Society Fact Sheet for more information about mesenchymal stem cells.

What is MESCAMS?

MESCAMS is a randomized, double-blind, cross-over, phase II clinical trial (that’s quite a mouthful, but I’ll explain what that means in a moment) investigating the safety and therapeutic potential of mesenchymal stem cell therapy for people with MS. The study will involve40 patients who will receive the treatment one at two sites – The Ottawa Hospital and Health Sciences Centre (HSC) Winnipeg.

One benefit of the study design is that it is an autologous stem cell procedure. A major advantage of autologous stem cell treatment is that the body’s immune system recognizes the cells as its own, and so the stem cells are not rejected by the body, a complication referred to as graft-versus-host-disease. In the case of MESCAMS, mesenchymal stem cells will be harvested from the bone marrow of study participants, multiplied in the laboratory over several weeks (a process known as culturing), and transplanted back into the participants via intravenous injection.

Another strong aspect of the study is its cross-over design. In a classic randomized controlled trial, participants are selected at random to receive either the intervention or a mock treatment (control or placebo) and they remain in those groups for the duration of the study. The purpose of involving an untreated control group is to determine if the treatment effect is real or due to a placebo effect.

The drawback to this study design is that one group of individuals does not receive a potentially beneficial treatment. In a cross-over design, on the other hand, all participants in the trial receive the stem cell therapy and the placebo at some point in the study; the only difference is the order in which they receive the two treatments. The early treatment group will be given a single infusion of their own mesenchymal stem cells at the start of the study, and then cross over 6 months later to receive the placebo. The late treatment group will be given a placebo infusion at the start of the study, then cross over 6 months later to be given the stem cell treatment. This way, all participants will serve as their own control group, and observations made in the early treatment group will shed light on any potential long-term effects of the stem cell treatment.

Both participants and investigators will be blinded to (i.e. unaware of) the treatment being administered at all times, which will eliminate any potential bias in the study. All participants will be monitored for throughout the year of treatment, and the investigators will be watching out for two things. The first is the safety of the procedure, which will be assessed by documenting any adverse health effects. The second is any potential clinical benefit of the treatment, which can include reductions in inflammatory injuries in the brain, fewer relapses, improved disability, and signs that repair to damaged nervous tissue is taking place.

Many people ask, “How does this study differ from the previous bone marrow stem cell study funded by the MS Society?” The key difference between MESCAMS and the Bone Marrow Transplantation (BMT) trial is that the purpose of transplanting autologous hematopoietic (blood cell-forming) stem cells in the BMT trial was to, in effect, “reboot” the immune system by repopulating it with new immune cells that don’t attack and damage the central nervous system. In order to accomplish this, participants in the trial were subjected to a risky and intensive chemotherapy procedure to first eliminate the existing immune system; as such, only participants with rapidly progressing forms of MS that did not respond to available therapies were considered for the trial due to its potentially serious side effects. In MESCAMS, mesenchymal stem cell therapy has the potential to suppress inflammation and promote repair of nervous tissue without the need to eliminate the immune system with chemotherapy, and so the risks to the participants are much smaller.

What’s Next?

The announcement of MESCAMS was met with an outpouring of hope and excitement by the MS community, but a great deal of work remains to be done and it will likely be several years before the results of the trial begin to flow in. Now that regulatory approvals are in place – including Health Canada clinical trial application and institutional research ethics approvals – screening and recruitment of participants can begin in earnest. Determining who is eligible to participate in the trial is done on the basis of detailed inclusion and exclusion criteria, and the screening process is carried out by the clinical trial coordinators at each of the two sites. The coordinators are also responsible for explaining all of the risks associated with the treatment, which is an important step before an individual consents to participating in the study.

To see who is eligible to participate in MESCAMS, and to find answers to any other questions you might have about the trial, take a look at our MESCAMS FAQ; anyone who is interested in participating should consult with their neurologist, who can then get in touch with the study coordinator at the appropriate site.

Do you have any thoughts on stem cell therapies? Share them with us and leave a comment below.

5 thoughts on “MESCAMS: A recap and what’s next?

  1. Michelle Hewitt

    Thanks for the explanation!

    How was the period of 6 months decided on for cross over? It just seems that we talk about an annual relapse rate that I wonder if that will give enough time for the participants MS to be active, or not!

    Reply
    1. drkarenlee Post author

      Hi Michelle,

      That’s a great question. In fact, the study design allows half of the participants to be followed for up to a year after treatment with mesenchymal stem cells. Although participants in the early treatment arm (the group that receives mesenchymal stem cells at the very start of the study) will cross-over to receive a placebo after 6 months, they will continue to undergo assessments for safety and efficacy throughout the year to determine the longevity of the treatment effect.

      Dr. K

      Reply
  2. Anonymous

    Didn’t the rest of the world that are way ahead of us here in Canada when it comes to anything medical already prove that these stem cells do not work and this is just another rip off so scientists here in Canada can get rich. I think Germany has been doing this since the 90s and there’s a reason it never made it past a phase two trial. If they really want to cure ms then they need to stop the hsv viruses from causing this devastating disease in the first place

    Reply

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