Rebalancing the immune system:
Myasthenia gravis is an autoimmune disorder in which the immune system mistakenly attacks the part of the muscle fiber that receives signals from the nerve fiber.
Myasthenia gravis occurs when the immune system makes antibodies that destroy the ACh receptor (AChR), a docking site for the nerve chemical acetylcholine (ACh). Some treatments block acetylcholinesterase (AChE), an enzyme that breaks down ACh, while others target the immune system. GM-CSF may modulate the immune system and reduce production of antibodies against the AChRs.
In MG, the immune system attacks acetylcholine receptors, the docking sites for the neurotransmitter acetylcholine. Acetylcholine activates muscle fibers at the neuromuscular junction, the place where nerve and muscle fibers meet.
The usual treatments for MG include drugs to increase levels of acetylcholine and drugs to suppress the immune system. Immunosuppressive drugs have toxic side effects, so it's desirable to minimize the dosage and duration of their use. Another treatment, plasmapheresis, is sometimes used to filter out antibodies that attack the receptors.
The experimental compound’s name, GM-CSF, stands for granulocyte-macrophage colony-stimulating factor.
A drug based on GM-CSF, sargramostim (brand name Leukine), has been approved by the U.S. Food and Drug Administration for use following chemotherapy or bone marrow transplantation for blood-cell cancers. In these circumstances, GM-CSF is used to stimulate recovery of the immune system after damage by cancer treatment.
In MG, the goal is to use GM-CSF to rebalance the immune system by stimulating proliferation of regulatory immune system cells that dampen an immune response, thereby moderating an immune system attack on acetylcholine receptors.
Meriggioli and colleagues have found that GM-CSF appears to mobilize immune regulatory cells and suppress disease symptoms in a mouse model of MG.
