Open Access Research

Treatment of dysferlinopathy with deflazacort: a double-blind, placebo-controlled clinical trial

Maggie C Walter1*, Peter Reilich1, Simone Thiele1, Joachim Schessl1, Herbert Schreiber2, Karlheinz Reiners3, Wolfram Kress4, Clemens Müller-Reible4, Matthias Vorgerd5, Peter Urban6, Bertold Schrank7, Marcus Deschauer8, Beate Schlotter-Weigel1, Ralf Kohnen9 and Hanns Lochmüller10

Author Affiliations

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

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Orphanet Journal of Rare Diseases 2013, 8:26  doi:10.1186/1750-1172-8-26

Published: 14 February 2013

Abstract

Background

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).

Methods

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.

Results

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.

Conclusion

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.

Trial registration

This clinical trial was registered at http://www.ClincalTrials.gov webcite, identifier: NCT00527228, and was always freely accessible to the public.

Keywords:
Limb girdle muscular dystrophy (LGMD); Dysferlinopathy; Therapy; Deflazacort; Muscle strength; Steroids