Findings on the immune response to dystrophin in Duchenne and Becker MD, treatment of cardiomyopathy in DMD, and eteplirsen in DMD were presented
|Update (June 1, 2012) — The brief Drugs help DMD-related cardiomyopathy has been updated to include a May 2012 podcast provided by Nationwide Children's Hospital's "This Month in Muscular Dystrophy."
The 2012 annual meeting of the American Academy of Neurology, being held in New Orleans April 21-28, included findings related to Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD).
Some DMD patients mount an immune response to the dystrophin protein when it's supplied via gene therapy because of pre-existing immunity to this protein. This response is a limiting factor in therapy development for DMD.
But corticosteroids may help suppress this unwanted immune response, reported Kevin Flanigan from Nationwide Children's Hospital in Columbus, Ohio, citing results of a new study supported by the National Institutes of Health (NIH).
The study included 76 people with DMD, six with BMD and 21 healthy children who served as a control group. Twenty-four of the DMD patients were taking the corticosteroid drug prednisone, and 29 the similar corticosteroid deflazacort. Seventeen of the DMD patients were not taking a corticosteroid medication.
The investigators found that:
The researchers concluded that:
A multicenter study supported in part by MDA and conducted by the MDA DMD Clinical Research Network has found that treatment of cardiomyopathy (deterioration of the heart muscle) in DMD with an ACE inhibitor alone, or with an ACE inhibitor plus a beta blocker, resulted in better heart function than no treatment.
Heart function was assessed by a series of echocardiograms measuring changes in ejection fraction, the amount of blood pumped out with each cardiac cycle (heartbeat). A normal ejection fraction is at least 55 percent.
ACE (angiotensin converting enzyme) inhibitors help relax blood vessels, reducing the workload on the heart. Beta (beta adrenergic receptor) blockers cause the heart to beat more slowly and with less force.
Philip Thrush from Nationwide Children's Hospital in Columbus, Ohio, presented the findings, which were also published online April 5, 2012, in the American Journal of Cardiology.
The 45 patients in this study who had DMD-related cardiomyopathy received either the ACE inhibitor lisinopril alone, or lisinopril plus the beta blocker metoprolol. Only those participants whose average heart rates were greater than 100 beats per minute received the beta blocker.
Twenty-four of the trial participants also were studied prior to any treatment, so that "natural history" data on the progression of DMD-related cardiomyopathy could be obtained.
The investigators found that:
Be sure to check out a May 2012 podcast provided by Nationwide Children's Hospital's "This Month in Muscular Dystrophy" in which pediatric cardiologist Hugh Allen, an investigator on the cardiomyopathy study, provides an in-depth discussion of the implications of the study.
Treatment with the experimental exon-skipping drug eteplirsen, in development by AVI BioPharma for patients with DMD who have mutations in or near exon 51 of the dystrophin gene, was recently shown to result in increased production of the dystrophin protein in muscle fibers but not to cause significant improvement in the distance walked in six minutes (six-minute walk test).
At the AAN meeting, neurologist Jerry Mendell from Nationwide Children's Hospital in Columbus, Ohio, principal investigator on this study, offered a more detailed analysis of the findings. (MDA provided supplemental support from this trial through Mendell.) A poster presentation supplemented Mendell's talk.
New information presented at the AAN meeting included the following:
For more on the eteplirsen findings, see the information posted April 25 on the AVI BioPharma site under Events & Presentations.