Neurologist James F. Howard Jr., from the University of North Carolina at Chapel Hill, presented positive results from a phase 2 pilot trial of eculizumab (Soliris) in people with severe, generalized (affecting muscles throughout the body) MG whose disease could not be adequately treated with at least two standard immunosuppressant medications for more than one year.
Eculizumab is a type of immunosuppressant known as a complement inhibitor. The drug is on the market to treat two conditions unrelated to MG (paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome).
This multicenter, double-blind, placebo-controlled study included 14 people who had moderate to severe muscle weakness despite treatment with immunosuppressants for more than a year.
Among the findings:
Neurologist Julie Rowin from the University of Illinois College of Medicine at Chicago described how the use of an experimental drug called GM-CSF may have contributed to an improvement in the condition of a 77-year-old man with a prolonged myasthenic crisis that was resistant to conventional treatments.
A myasthenic crisis involves MG-related weakening of the respiratory muscles so that breathing is not possible without mechanical ventilation.
There is evidence that GM-CSF (granulocyte-macrophage colony-stimulating factor) can "rebalance" the immune system by stimulating cells that dampen (regulate) an immune response. These cells are known as T regulatory cells, or Tregs. (MG involves an inappropriate immunologic attack on the place where nerve and muscle fibers meet, and dampening this immune response would presumably improve the disease course.)
GM-CSF (also known as sargramostim and marketed by Genzyme as Leukine) is approved by the U.S. Food and Drug Administration for use after chemotherapy to improve the white blood cell count and for use during harvesting of peripheral blood stem cells to be used for bone marrow transplantation. MDA is supporting the development of this drug for possible use in MG.
Experiments in mice with an MG-like disease have shown that GM-CSF can suppress a misdirected immune response and expand the number of functional Tregs.
Prior to treatment with GM-CSF, the Tregs of the patient in this one-person study were not optimally functional. After the treatment, there was an increase in the number of functional Tregs and in their ability to suppress an immune response. This coincided with an improvement in the patient's clinical status.
The investigators reached several conclusions:
In an April 30, 2012, email to Quest, Julie Rowin said the patient in this study has regained the ability to breathe on his own and is now in remission on 1,000 milligrams per day of the immunosuppressant mycophenolate. He has resumed his usual activities, including square dancing and mowing the lawn.
However, she noted, "I just don't think we have the data to say that his clinical improvement is clearly or solely due to the GM-CSF, since he was on multiple treatments concurrently."