The Future of Myasthenia Gravis
Prolonged drug treatment is known to carry potentially severe risks.
The goal amongst researchers developing treatments and therapies for MG is erradication of the autoimmune response and to regain tolerance without adverse effects to the patients immune system i.e. dangerous levels of immunosupression.
This will require furthered research into the molecular immunology of Myasthenia Gravis.
Outlined below are some potentially new approaches to the treatment of MG.
Granulocyte Macrophage Colony Stimulating Factor (GM-CSF):
A study was conducting using dendritic cells to tolerize lymphocytes to antigens (Merrigioli et al, 2006).
The state of differentiation of dendritic cells was found to influence tolerization of T Cells. GM-CSF treated mice exhibited marked supression of induction of experimental MG in mice, indicated by:
- Decrease in serum autoantibody levels
- Decrease in T-Cell response
Orchestrator of the study, Professor Matthew Merrigioli, has recently been awarded funding to move research into GM-CSF towards clinical trials, making way for multi-centre trials to investigate the drugs effectiveness in Myasthenia Gravis sufferers.
A great deal of energy and resources have been focused upon the improvement of current treatment methods; ways of enhancing the scheme of treatment available as the diseases advances (i.e. initially cholineresterase inhibitors, progressing to immuno-modulatory pharmaceuticals for severe weakness).
A review of the therapeutic options available to treat Myasthenia Gravis (García-Carrasco et al, 2006) came to a number of conclusions:
- Further clinical trials should be conducted to try and establish the best use of current pharmaceuticals in certain subgroups and poorly controlled myasthenia gravis
- To identify new or modify existing agents with increased efficacy, as to reduce adverse effects on the immune system
A study investigating the effectiveness of bacterially expressed human muscle AChR cytoplasmic domains in an animal model of Myasthenia Gravis (EIMG) (Luo et al, 2010), indicates a future as a novel therapy:
- Rats were given the AChR constructs via intraperitoneal injection for a 5 week period
- Found that MG was supressed in the rats
- Autoantibody production directed away from extracellular domain to the cytoplasmic domain
By shifting the pathological focus of the auto-antibodies to the AChR 'free' in the interstitial fluid, there is a reduction in antibody targeting of the AChR that remain intact in the NMJ. This reduced the symptoms of EIMG demonstrated by the rats.
Using a epitope with little pathological relevance also reduces the possibility of enhancing the disease response to relevant epitopes. This means the chances of enhancing the disease response are minimal.
The study concluded the use of antigen-specific immunotherapy has the potential to be an effective therapy for MG, whilst further investigation is required.
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