Multiple Sclerosis Scientific Research Foundation funded study advances understanding of risky but effective stem cell treatment

Background – Stem cell therapies in MS

Stem cells are unique cells in the body which possess the capability to ‘self-renew’, or replicate themselves, as well as develop into specialized cells which perform specific functions. These characteristics have identified stem cells as a potential treatment option for diseases like MS, where cells are damaged and need to be replaced to restore function in the body.

Hematopoietic stem cells (HSCs) are stem cells that originate in the bone marrow and mature into different blood and immune cells. It is believed that HSCs are capable of treating patients with MS by developing into immune cells that are not damaging to the central nervous system.

Treatment with HSCs is a risky procedure and therefore only used for rapidly progressive forms of MS that do not respond to available therapies. In 2000, the Multiple Sclerosis Scientific Research Foundation funded a multi-centre project examining the therapeutic potential of HSCs in MS. Referred to as the Canadian Bone Marrow Transplantation (BMT) trial, the project is led by Drs. Mark Freedman and Harry Atkins at the Ottawa Hospital Research Institute. Outcomes of the trial revealed patients being relapse free up to 2 years after bone marrow transplantation as indicated by clinical examination and brain MRI scans.

Currently they are conducting a follow up study to determine the long term consequences of stem cell therapy on MS outcomes. The extended phase includes new MRI scans, comprehensive clinical evaluations, and immunological experiments.

The Canadian BMT trial as well as the follow-up immunological studies conducted by Dr. Amit Bar-Or and colleagues were recently published online in Annals of Neurology. Dr. Bar-Or serves as the Director of the Experimental Therapeutics Program and Scientific Director of the Clinical Research Unit, at the Montreal Neurological Institute (The Neuro) at McGill.

The studies:

The phase II BMT trial included 24 patients that underwent intense chemotherapy to suppress the immune system followed by stem cell transplantation. Following treatment, investigators observed diminished relapse activity, absence of lesions on MRI, and significant improvements in brain function. The positive results yielded from this high-risk but effective procedure prompted a follow-up investigation to determine the longevity of the response.

One component of the follow-up study, involved a series of immunological experiments aimed to determine the function of restored T cells following post transplantation blood was collected and analyzed from 14 patients initially enrolled in the BMT trial. All of the patients had highly aggressive forms of MS and were between 26-41 years of age.

What they found:

Earlier results on the immunological studies by Dr. Bar-Or’s team confirmed the absence inflammatory MS disease, which has been sustained years after therapy and without any ongoing treatment. They also discovered that functioning of the thymus – the organ where T cells mature – as well as circulating levels of T cells restored to almost normal levels following therapy. T cell subgroups derived from the transplanted HSCs exhibited autoreactive activity. They determined that the autoreactive T helper cells are of the Th1 and Th2 subgroups. These subgroups have been shown to play a role in MS by releasing toxic agents and recruiting other immune cells which also contribute to tissue damage. Interestingly, they observed a marked decrease in levels of Th17 cells compared to levels before treatment. Researchers postulate that the absence of new relapsing disease activity following BMT may be associated with diminished Th17 cell activity, which fits well with the previously demonstrated notion that Th17 cells are considered ‘gatekeepers’ to the CNS and thus facilitate the entry of harmful Th1 and Th2 cells into the brain.


The beneficial health outcomes observed from the Canadian BMT trial left researchers with questions on whether the patients will remain disease-free over a longer period, and what immunological changes are associated with observed long-term effects. Dr. Bar-Or’s research in conjunction with the work of the lead investigators provides important insight into how new relapses develop in MS, while adding to ongoing evidence on the role of Th17 cells in in autoimmune responses. This finding enhances our understanding of MS, and could lead to modifications to stem cell therapies to achieve long-term remission while minimizing risk.

Source: Darling PJ et al. Diminished Th17 (Not Th1) Responses Underlie Multiple Sclerosis Disease Abrogation after Hematopoietic Stem Cell Transplantation. Annals of Neurology, 2012 Oct 11