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

Orphanet Journal of Rare Diseases

Hanns Lochmüller³  Ralf Kohnen⁸  Beate Schlotter-Weigel⁹  Marcus Deschauer¹  Bertold Schrank⁶  Peter Urban^1,10  Matthias Vorgerd⁴  Clemens Müller-Reible⁵  Wolfram Kress⁵  Karlheinz Reiners²  Herbert Schreiber⁷  Joachim Schessl⁹  Simone Thiele⁹  Peter Reilich⁹  Maggie C Walter⁹ 

[1] Department of Neurology, University Halle-Wittenberg, Halle, Germany;Department of Neurology, University of Würzburg, Würzburg, Germany;Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, UK;Department of Neurology, Neuromuscular Center Ruhrgebiet, Ruhr-University Bochum, Bochum, Germany;Department of Human Genetics, Biozentrum, University of Würzburg, Würzburg, Germany;Department of Neurology, Deutsche Klinik für Diagnostik, Wiesbaden, Germany;Neuropoint Patient Academy, Ulm, Germany;RPS Research Germany GmbH, Nürnberg, Germany;Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University of Munich, Ziemssenstr. 1a, Munich, 80336, Germany;Department of Neurology, Asklepios Klinik Barmbek, Hamburg, Germany

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

Others  :  864120
DOI  :  10.1186/1750-1172-8-26

 received in 2012-10-29, accepted in 2013-02-10,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Walter et al.; licensee BioMed Central Ltd.

【 图 表 】

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