Senior Scientist, Neuroscience, Ottawa Hospital Research Institute
Professor of Medicine (Neurology), University of Ottawa
Director, Multiple Sclerosis Research Unit, The Ottawa Hospital-General Campus
Research Interests
Neuroimmunology as applied to the study of MS
Clinical MS research
Therapeutic trials in MS
Major Research Activities
ASCT as a potential treatment for MS
The role of gamma delta T cells in the pathogenesis of MS
The role of cytokines in MS disease progression or response to therapy
Current and Future Research
Multiple sclerosis research has been exploding in recent years with the advent of new tools both in neuroscience and immunology to further our understanding of the disease. My own focus of research has been concentrated in 3 areas:
Basic Neuroimmunology
With 2 PhD students, one nearly finished and the other nearly starting, this is still an active area. Both projects revolve around my focus for the past decade on the innate immune system and in particular, gd T cells . Work done mostly by Zhihong Chen has examined a unique feature of these cells to cytolyse cells using the mechanism of antibody-dependent cell cytotoxicity via their Fc receptors. His work has revealed that patients particularly with the progressive phase of their illness display the greatest number of Fc bearing gd T cells. Research has revealed also a number of antibodies to myelin that may be playing a role at this stage and our hypothesis is that these antibodies can direct gd T cells to injure oligodendrocytes. In collaboration with Dr. Jack Antel at the MNI, Zhihong has shown this to be the case.
In a separate project together with Peter Stys, Jennifer Beveridge is concentrating on a model of in vitro demyelination that Peter and I developed together, wherein we can inject cells generated in my laboratory directly into a rat optic nerve and watch how they cause damage to myelin and axons. Jennifer has chosen to move to Calgary for the first couple of years of this project and then to return here for the latter part to work with the immune cells.
Clinical Investigator-Driven Research
Together with Harry Atkins, our work on the Canadian bone marrow transplantation has gained international notoriety. Our observations have been seminal and has generated many new observations not only clinically, but through the vast imaging and immunological monitoring developed in conjunction with our colleagues, to follow this unique group of patients who undergo autologous stem cell transplantation following complete immune ablation. We have recently received a new grant from the MS Foundation to examine, in particular, some of our observations that the disease is not only halted following this treatment, but some patients make some miraculous recovery, suggesting repair of the CNS. We have hypothesized several mechanisms that might explain this phenomenon and have laid out a series of studies to help substantiate these.
In a separate and new venture, Harry and I are working on developing a new technology to try on our more progressive patients; that of mesenchymal stem cell (MSC) transplantation. These cells would not require a complete immune ablation such that patients will be spared the morbidity of that procedure. Together with a world renowned scientist in Montreal for his work on growing MSC we hope to have a viable protocol that can be brought to clinical testing within the year.
Clinical Industry-Driven Research
It would appear that there is no end to new studies with a vast array of new agents that bring to the table less morbidity and novel targeted immune therapies, from small molecules aimed at controlling either the expression of a receptor or the release of cytokines, to more focused monoclonal antibody treatments. Studies are now focusing on all phases of MS including the more later stages with agents that might be capable of regeneration or repair. As a member of many steering committees and consultant to several companies, I have been assisting in the development of these trials and hope to keep TOH at the forefront of MS research.
Recent Publications
Key Words:
Multiple Sclerosis
( Dr. Mark Freedman, Neurologist, Ottawa, ON) is in good standing with the College of Physicians and Surgeons.
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