Treatment of dysferlinopathy with deflazacort: a double-blind, placebo-controlled clinical trial
- Equal contributors
1 Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University of Munich, Ziemssenstr. 1a, Munich, 80336, Germany
2 Neuropoint Patient Academy, Ulm, Germany
3 Department of Neurology, University of Würzburg, Würzburg, Germany
4 Department of Human Genetics, Biozentrum, University of Würzburg, Würzburg, Germany
5 Department of Neurology, Neuromuscular Center Ruhrgebiet, Ruhr-University Bochum, Bochum, Germany
6 Department of Neurology, Asklepios Klinik Barmbek, Hamburg, Germany
7 Department of Neurology, Deutsche Klinik für Diagnostik, Wiesbaden, Germany
8 Department of Neurology, University Halle-Wittenberg, Halle, Germany
9 RPS Research Germany GmbH, Nürnberg, Germany
10 Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, UK
Orphanet Journal of Rare Diseases 2013, 8:26 doi:10.1186/1750-1172-8-26Published: 14 February 2013
Dysferlinopathies are autosomal recessive disorders caused by mutations in the dysferlin (DYSF) gene encoding the dysferlin protein. DYSF mutations lead to a wide range of muscular phenotypes, with the most prominent being Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B).
We assessed the one-year-natural course of dysferlinopathy, and the safety and efficacy of deflazacort treatment in a double-blind, placebo-controlled cross-over trial. After one year of natural course without intervention, 25 patients with genetically defined dysferlinopathy were randomized to receive deflazacort and placebo for six months each (1 mg/kg/day in month one, 1 mg/kg every 2nd day during months two to six) in one of two treatment sequences.
During one year of natural course, muscle strength declined about 2% as measured by CIDD (Clinical Investigation of Duchenne Dystrophy) score, and 76 Newton as measured by hand-held dynamometry. Deflazacort did not improve muscle strength. In contrast, there is a trend of worsening muscle strength under deflazacort treatment, which recovers after discontinuation of the study drug. During deflazacort treatment, patients showed a broad spectrum of steroid side effects.
Deflazacort is not an effective therapy for dysferlinopathies, and off-label use is not warranted. This is an important finding, since steroid treatment should not be administered in patients with dysferlinopathy, who may be often misdiagnosed as polymyositis.