MGFI Sponsored Research       

One of the most exciting and  rewarding activities of the MGFI is sponsoring research projects for the treatment and potential cure of MG.  Many such projects have been conducted in the past and more are planned for the coming years.  Here is a brief description of a few of the current and recent studies and activities:

Etanercept Study. The MGFI has announced $25,000.00 funding for a study on the use of Etanercept in MG. 

This study will evaluate if a medication that is injected under the skin twice-a-week called etanercept (Enbrel®) is a safe and effective treatment for patients with myasthenia gravis who are dependent on corticosteroid treatment for control of their disease. Etanercept is currently approved by the Food and Drug Administration for the treatment of rheumatoid arthritis and has been shown to be effective treatment for this disease. The goal of the study is to determine if etanercept treatment is safe and effective for patients with myasthenia gravis and if etanercept will allow patients with myasthenia gravis to decrease or discontinue treatment with corticosteroids (prednisone).

Dr. Meriggioli and Dr. Rowin studied etanercept in a small number of patients with myasthenia gravis, and this small study suggested that etanercept may be beneficial for some patients with myasthenia. Eleven patients who were dependent on corticosteroids to control their disease were enrolled in this study.  Three subjects were taken out of the study before it was completed, two because their myasthenic symptoms worsened and one because of the development of a rash.  Therefore, out of the eight patients who completed the study, six patients improved and two patients were unchanged. We concluded that it would be useful to do a larger study to look more thoroughly at the effectiveness of this treatment.

Etanercept works by blocking TNF-α (tumor necrosis factor alpha).  TNF-α is thought to play a significant role in the disease process of myasthenia gravis.  The theory of treatment with etanercept is that by blocking TNF-α, etanercept will decrease disease activity allowing the patient to become stronger and require less prednisone.

This study will enroll 38 patients with myasthenia gravis who have acetylcholine receptor antibodies present in the blood.  The first part of the study will last 6 months.  During this phase of the study, half of the patients will receive etanercept treatment and half will receive placebo treatment.  The physicians and nurses examining the patients will not have knowledge as to who is on treatment with etanercept and who is on placebo treatment.  This way, there will be less bias in the results comparing the etanercept treated patients to the placebo treated patients. The second part of the study also lasts 6 months, but this time every patient receives etanercept and there is no placebo given.  The patients have an option whether to participate in the second six month part of the study or not.  Again, all patients will be evaluated monthly.

Monitoring safety is the priority of this study.  Although etanercept has been approved by the Food and Drug Administration (FDA) for use in rheumatoid arthritis, patients on etanercept, as with all immunosuppressive agents, are at risk of developing serious adverse reactions (see protocol 12.2 risks to subjects). We have a plan in place that is aimed at preventing and minimizing adverse reactions.  We will form an independent Data and Safety Monitoring Committee made up of physicians whose sole purpose will be to monitor the safety of the study and determine if the study should be changed or stopped because of safety reasons.  There is also an independent physician called a medical monitor who will ensure that the protocol is designed to adequately evaluate the safety of etanercept.

Other information will be collected from the patients in this study that will help us understand myasthenia gravis better.  For example, blood will be collected to measure the level of different inflammatory proteins in the blood and the acetylcholine receptor antibody levels in the blood. Examining these inflammatory proteins may give us better insight into how the disease works.

The goal is to see other treatments become available for myasthenia gravis patients which are safe and effective without the long-term side-effects of prednisone.  Our hypothesis of this study is that etanercept is a safe and effective treatment for myasthenia gravis.

Osserman and Viet Fellowships.  At the 2005 MGFA Annual Meeting in Grand Rapids, MI, the MGFI provided funding for a $50,000.00 Osserman Fellowship to the MGFA.  Funding for three Viet Fellowships ($9,000.00) was also announced and will be presented when candidates are available.  See the Myasthenia Gravis Foundation of America site for more details on these fellowships.

Mary Prokop Research Grant.  Awarded to Dr. Arnason of the University of Chicago October 23, 2004.  The following is a lay summary of the work proposed. 

Intravenous immunoglobulin (IV IgG) is widely used to treat MG.  Massive doses are given indicating that some minor component in IV IgG preparations is responsible for its beneficial effect. 95-98% of the IgG consists of single molecules in solution. 2-5% consists of IgG in small clumps. Our hypothesis is that the small clumps are what matters. It turns out that cells of the immune system have receptors for clumped IgG but they do not have receptors for single IgG molecules. One cell type with receptors for clumped IgG is the macrophage. When IgG clumps bind to macrophages they cause the macrophages to shut down the synthesis of tissue damaging proteins, including a protein called IL-12 that is known to be a major contributor to muscle damage in the animal model disease for MG called Experimental Autoimmune Myasthenia Gravis (EAMG). IL- 12 is almost surely involved in MG as well. It turns out that a small section of the IgG molecule, about 10% of the molecule, contains the binding site for macrophages. This site is called the CH2 domain. Based on our hypothesis, we have genetically engineered a single soluble molecule that contains 10 CH2 domains lined up in 2 rows. It looks like an IgG clump to macrophages and it shuts down their production ofIL-12 by 95%. It turns out to be about 50 times as potent at this as IgG clumps. We propose to test it in EAMG. If it shuts down the disease, as we think it well may, then we would hope to bring it along as a new, improved, simple, and fast treatment for MG.

Terbutaline.  A randomized  double blind placebo controlled crossover study to assess the effacy of Terbutaline in patients with MG was conducted.  The results need further confirmation but it was concluded that Terbutaline is probably an effective adjunct therapy in some patients with MG. 

Cell Cept.  This study which was partially funded by the MGFI examined the use of Cell Cept in patients with sub optimally treated MG.  Patients treated with Cell Cept improved compared to placebo on all four measures of effectiveness.   A large multi center trial of Cell Cept as therapy of MG is planned.  Results were presented at the Tenth International Conference on MG in June 2002.

Recombinant Protein Study.  Antibodies complexed to the muscle side of the nerve-muscle junction attract blood monocytes that attack the complexes thus contributing to tissue damage.  The monocytes also release products known as cytokines that unfavorably alter the electrical properties of the muscle membrane and this contributes to weakness.   The goal of this therapeutic approach is to "turn off" the monocytes.

Tenth International Conference on MG and Related Disorders. The MGFI provided significant financial support for holding this Conference which is sponsored by the NY Academy of Sciences and the MGFA.  It is held every five years.  Physicians and researchers from 26 countries gathered to share research findings and to set the direction for MG research over the next five years.  The MGFI sponsored CellCept study, mentioned above, was presented at the Conference.

Volunteer participants needed!  Patients are always needed and are in short supply for studies of new MG treatments.  If you would like to participate in one of the upcoming studies please contact our office. See Volunteer for Details

Donate. If you can't participate in a study you can still help out by contributing to study expenses.  We accept donations of any size and they can be targeted for research use only.  And, of course, all donations are tax deductible.  See MGFI Donations

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