Multiple Sclerosis Group Current Research
Project One: Evaluating the Therapeutic Potential of Exploiting Regulatory T Cells to Treat MS
Regulatory T cells are specialised immune cells that play a crucial role in controlling immune responses and preventing autoimmune disease. It has been shown previously that the function of regulatory T cells is altered in patients with MS, such that they are unable to adequately turn off disease-causing self-reactive T cells.
We are investigating the cellular and molecular mechanisms involved in the restoration of functionality and activation of regulatory T cells in experimental autoimmune encephalomyelitis (EAE), a well established murine model of human MS.
The goal of this research is to examine the therapeutic potential for exploiting regulatory T cell activity in the treatment of patients with MS.
In 2008 we successfully generated functional regulatory T cells that possessed integrin molecules. These results suggest that the cells have the ability to migrate to sites of inflammation, and as such, can be used to effectively inhibit experimental MS.
Project Two: The Use of Immunosuppressive Cells to Inhibit EAE
A potent suppressor cell type has been identified that exists as part of the normal immune cell population. These cells are capable of limiting CD4+ T cell responses and are therefore another potential target for the development of therapies to treat autoimmune diseases such as MS.
Using the EAE murine model of human MS, we have discovered that although suppressor cells are present in symptomatic animals, these cells do not possess suppressive activity.
We have identified a compound that appears to have a natural affinity for these suppressor cells and have shown that binding of the compound to this population of cells enhanced their suppressive activity.
When administered in vivo, the compound both restored the suppressive activity of the target cells and prevented the development of EAE.
These findings have important clinical implications for the design of novel immunotherapies for the treatment of individuals with MS.
Project Three: Targeting Antigen Presenting Cells to Treat Autoimmune Inflammation
The drug Glatiramer acetate (GA) is currently in clinical use for the treatment of patients with relapsing-remitting MS.
GA is a synthetic mimic of the myelin basic protein that surrounds and protects the nerve fibres of the central nervous system. It is not known exactly how GA works, but it is thought to protect the myelin sheath from T cell mediated damage by acting as a decoy.
We are attempting to further elucidate the suppressive mechanism of GA by identifying the cell type(s) that the drug primarily acts on in vivo.
Using our experimental models we have shown that GA is taken up by monocytes after intravenous injection. Interestingly, monocytes exposed to GA demonstrated increased intrinsic T cell suppressive activity, pointing towards a potential mechanism for the observed protective effects of GA.
This information will be vital for the development of strategies that target GA to specific cell types, in order to make the drug more effective.
Collaborators
Prof Claude Bernard, Monash University, Melbourne, Australia
Prof John Fraser, The University of Auckland, New Zealand
Dr Ian van Driel, University of Melbourne, Australia
Funding Sources
Health Research Council of New Zealand
New Zealand Lottery Health Research
Nikau Foundation (previously Wellington Region Foundation)
Wellington Medical Research Foundation
