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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2013

Open Access 01-12-2013 | Research

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

Authors: Maggie C Walter, Peter Reilich, Simone Thiele, Joachim Schessl, Herbert Schreiber, Karlheinz Reiners, Wolfram Kress, Clemens Müller-Reible, Matthias Vorgerd, Peter Urban, Bertold Schrank, Marcus Deschauer, Beate Schlotter-Weigel, Ralf Kohnen, Hanns Lochmüller

Published in: Orphanet Journal of Rare Diseases | Issue 1/2013

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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, identifier: NCT00527228, and was always freely accessible to the public.
Appendix
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Metadata
Title
Treatment of dysferlinopathy with deflazacort: a double-blind, placebo-controlled clinical trial
Authors
Maggie C Walter
Peter Reilich
Simone Thiele
Joachim Schessl
Herbert Schreiber
Karlheinz Reiners
Wolfram Kress
Clemens Müller-Reible
Matthias Vorgerd
Peter Urban
Bertold Schrank
Marcus Deschauer
Beate Schlotter-Weigel
Ralf Kohnen
Hanns Lochmüller
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2013
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/1750-1172-8-26

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