title: Treatment of dysferlinopathy with deflazacort: a double-blind, placebo-controlled clinical trial.
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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  This clinical trial was registered at http://www.ClincalTrials.gov, identifier: NCT00527228, and was always freely accessible to the public.
authors: Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University of Munich, Ziemssenstr. 1a, Munich 80336, Germany. maggie.walter@lrz.uni-muenchen.de
authors: Maggie C
authors: MC
authors: Walter
authors: Peter
authors: P
authors: Reilich
authors: Simone
authors: S
authors: Thiele
authors: Joachim
authors: J
authors: Schessl
authors: Herbert
authors: H
authors: Schreiber
authors: Karlheinz
authors: K
authors: Reiners
authors: Wolfram
authors: W
authors: Kress
authors: Clemens
authors: C
authors: Müller-Reible
authors: Matthias
authors: M
authors: Vorgerd
authors: Peter
authors: P
authors: Urban
authors: Bertold
authors: B
authors: Schrank
authors: Marcus
authors: M
authors: Deschauer
authors: Beate
authors: B
authors: Schlotter-Weigel
authors: Ralf
authors: R
authors: Kohnen
authors: Hanns
authors: H
authors: Lochmüller
mesh_terms: D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D053580:Muscle Strength; D049288:Muscular Dystrophies, Limb-Girdle / Q000188:drug therapy* / Q000503:physiopathology; D010919:Placebos; D011282:Pregnenediones / Q000627:therapeutic use*; D011788:Quality of Life; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D010919:Placebos; D011282:Pregnenediones; C021988:deflazacort