Hope Through Research

At MDA, we take a big picture perspective across the full spectrum of neuromuscular diseases to uncover scientific and medical breakthroughs that accelerate treatments and cures. The power in our research approach is that we can often apply learnings from one disease to progress in others to bring urgently-needed answers to our families.

Myasthenia Gravis (MG)

Myasthenia gravis (MG) is an autoimmune disease, in which the body’s own immune system attacks proteins at the neuromuscular junction (NMJ). Different forms of MG are due to attack on different NMJ proteins. The neuromuscular junction is the place on the surface of the muscle where it is contacted by a motor neuron. The tip of the motor neuron, called the axon terminal, releases a chemical neurotransmitter, called acetylcholine (uh-SEE-tul-KO-leen, abbreviated Ach). The Ach then binds to a protein on the muscle surface, called the acetylcholine receptor. This triggers muscle contraction. Another junction protein, called muscle-specific kinase (MuSK) helps create the structure of the NMJ during development. Both proteins are targets for the immune system in MG.

Antibodies form against NMJ proteins

The immune system has multiple parts, and uses multiple strategies to detect and inactivate what it views as foreign or harmful. A key weapon in the immune system is an antibody, created by B cells. An antibody is a protein whose shape fits that of its target, in the way that a key fits a lock or a hand fits a glove, allowing it to bind to the target. In about 85% of people with MG, the immune system attacks the Ach receptor. In about 5% of patients, the attack is on MuSK. Another protein, called LRP4, is the target in a fraction of the other patients, while the target remains unknown in others.

Besides B cells, the immune system includes T cells, which regulate the system, and complement, a set of proteins that attack cells marked for destruction. Each of these is also a potential therapeutic target in MG.

Therapeutic strategies

There are several well-developed and important therapies for MG that allow many patients to live their lives largely unimpaired by their disease. These include cholinesterase inhibitors (which prolong the effect of acetylcholine at the NMJ), immunosuppressants, removal of antibodies from the bloodstream (called plasmapheresis) and intravenous immunoglobulin, which temporarily modulates the immune response. Early MDA research provided the basis for development of many of these therapies. Research continues to develop better treatments, and treatments for the less common forms (which generally do not respond as well to current therapies). Research also focuses on better understanding of the basis of the disease in order to find new therapeutic options.

Specific therapeutic strategies being explored are immunomodulation with growth factors, hematopoietic stem cell therapy, NMJ-specific immunosuppressants, complement-directed therapies, more effective immunosuppressants, and reducing acetylcholinesterase activity.

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