MDA Awards Grant to Test Potential MG Treatment

MDA’s translational research program has announced it is funding research into a potential treatment for the autoimmune disorder myasthenia gravis (MG).

The grant of $530,480 to University of Illinois-Chicago professor Matthew Meriggioli will fund a three-year study of an immune system modulator called GM-CSF. The compound will be tested in a mouse model of MG and in a small group of human subjects.

“MDA is pleased to support this important research to determine the potential of this compound to treat myasthenia gravis,” said Jane Larkindale, head of MDA’s translational research program. 

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.

About the MDA grant

Building on his previous work, Meriggioli plans to use this award to move GM-CSF through the early stages of translational research and toward human clinical trials.

Funding will be disbursed as milestones toward this goal are reached. These milestones include:

  • determining the duration of the drug’s effect in mice;
  • determining the optimal dose and route of administration of GM-CSF;
  • determining biomarkers that demonstrate the drug’s effect; and
  • laying the groundwork and conducting a small clinical trial involving four human subjects with MG.

Meaning for people with MG

This study will set the stage for a multicenter trial of GM-CSF that will determine the drug’s usefulness in treating MG.

Should the drug be shown to be safe in humans, at least one biotech company has expressed interest in developing it for use in MG. The fact that Leukine is already on the market for other uses saves some steps in the development process.

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