TY  - JOUR
A1  - Walter, Maggie C.
A1  - Reilich, Peter
A1  - Thiele, Simone
A1  - Schessl, Joachim
A1  - Schreiber, Herbert
A1  - Reiners, Karlheinz
A1  - Kress, Wolfram
A1  - Müller-Reible, Clemens
A1  - Vorgerd, Matthias
A1  - Urban, Peter
A1  - Schrank, Bertold
A1  - Deschauer, Marcus
A1  - Schlotter-Weigel, Beate
A1  - Kohnen, Ralf
A1  - Lochmüller, Hans
T1  - Treatment of dysferlinopathy with deflazacort: a double-blind, placebo-controlled clinical trial
JF  - Orphanet Journal of Rare Diseases
N2  - 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.
KW  - Deflazacort
KW  - muscle strength
KW  - gridle muscular-dystrophy
KW  - Duchenne dystrphy
KW  - Miyoshi myopathy
KW  - mutation
KW  - prednisone
KW  - gene
KW  - 2B
KW  - children
KW  - design
KW  - steroids
KW  - therapy
KW  - dysferlinopathy
KW  - Limb girdle muscular dystrophy (LGMD)
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125663
SN  - 1750-1172
VL  - 8
IS  - 26
ER  - 
TY  - JOUR
A1  - Dupuis, Luc
A1  - Dengler, Reinhard
A1  - Heneka, Michael T.
A1  - Meyer, Thomas
A1  - Zierz, Stephan
A1  - Kassubek, Jan
A1  - Fischer, Wilhelm
A1  - Steiner, Franziska
A1  - Lindauer, Eva
A1  - Otto, Markus
A1  - Dreyhaupt, Jens
A1  - Grehl, Torsten
A1  - Hermann, Andreas
A1  - Winkler, Andrea S.
A1  - Bogdahn, Ulrich
A1  - Benecke, Reiner
A1  - Schrank, Bertold
A1  - Wessig, Carsten
A1  - Grosskreutz, Julian
A1  - Ludolph, Albert C.
T1  - A Randomized, Double Blind, Placebo-Controlled Trial of Pioglitazone in Combination with Riluzole in Amyotrophic Lateral Sclerosis
JF  - PLoS One
N2  - Background: Pioglitazone, an oral anti-diabetic that stimulates the PPAR-gamma transcription factor, increased survival of mice with amyotrophic lateral sclerosis (ALS). 
Methods/Principal Findings: We performed a phase II, double blind, multicentre, placebo controlled trial of pioglitazone in ALS patients under riluzole. 219 patients were randomly assigned to receive 45 mg/day of pioglitazone or placebo (one: one allocation ratio). The primary endpoint was survival. Secondary endpoints included incidence of non-invasive ventilation and tracheotomy, and slopes of ALS-FRS, slow vital capacity, and quality of life as assessed using EUROQoL EQ-5D. The study was conducted under a two-stage group sequential test, allowing to stop for futility or superiority after interim analysis. Shortly after interim analysis, 30 patients under pioglitazone and 24 patients under placebo had died. The trial was stopped for futility; the hazard ratio for primary endpoint was 1.21 (95% CI: 0.71-2.07, p = 0.48). Secondary endpoints were not modified by pioglitazone treatment. Pioglitazone was well tolerated. 
Conclusion/Significance: Pioglitazone has no beneficial effects on the survival of ALS patients as add-on therapy to riluzole.
KW  - ALS
KW  - transgenic mouse model
KW  - central nervous system
KW  - nonalcoholic steatohepatitis
KW  - PPAR-gamme
KW  - hexanucleotide repeat
KW  - disease progression
KW  - delays progression
KW  - SOD1 mutations
KW  - monocycline
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130255
VL  - 7
IS  - 6
ER  -