PURPOSE: Duchenne muscular dystrophy (DMD) is a severe and fatal neuromuscular disease. With the current developments on novel therapeutic strategies for DMD, the need to carefully monitor disease progression or regression upon treatment using molecular markers has become urgent. EXPERIMENTAL DESIGN: 2D LC protein fractionation was performed on patient serum samples, followed by LC-MS/MS-based identifications with label-free quantifications. RESULTS: Protein signatures were compared between patients and healthy (child and adult) controls and between ambulant and nonambulant patients. Various myofibrillar proteins demonstrated differences between DMD patients and controls, likely due to leakiness and breakdown of muscle fibers. Previously reported biomarkers, such as muscle-derived titin, myosin, and carbonic anhydrase I (CA1), were verified. MS-based results were compared with ELISA for vitamin D binding protein (GC), fibulin-1 (FBLN1), gelsolin (GSN), and carbonic anhydrase 1 (CA1). CONCLUSIONS AND CLINICAL RELEVANCE: The combined results of MS- and ELISA-based quantifications indicated more studies are needed to validate this serum protein signature for DMD patients. With these data promising candidate biomarkers have been identified for a rare genetic disease using serum proteome analysis.
PURPOSE: Duchenne muscular dystrophy (DMD) is a severe and fatal neuromuscular disease. With the current developments on novel therapeutic strategies for DMD, the need to carefully monitor disease progression or regression upon treatment using molecular markers has become urgent. EXPERIMENTAL DESIGN: 2D LC protein fractionation was performed on patient serum samples, followed by LC-MS/MS-based identifications with label-free quantifications. RESULTS: Protein signatures were compared between patients and healthy (child and adult) controls and between ambulant and nonambulant patients. Various myofibrillar proteins demonstrated differences between DMD patients and controls, likely due to leakiness and breakdown of muscle fibers. Previously reported biomarkers, such as muscle-derived titin, myosin, and carbonic anhydrase I (CA1), were verified. MS-based results were compared with ELISA for vitamin D binding protein (GC), fibulin-1 (FBLN1), gelsolin (GSN), and carbonic anhydrase 1 (CA1). CONCLUSIONS AND CLINICAL RELEVANCE: The combined results of MS- and ELISA-based quantifications indicated more studies are needed to validate this serum protein signature for DMD patients. With these data promising candidate biomarkers have been identified for a rare genetic disease using serum proteome analysis.
Authors: Thomas Fröhlich; Elisabeth Kemter; Florian Flenkenthaler; Nikolai Klymiuk; Kathrin A Otte; Andreas Blutke; Sabine Krause; Maggie C Walter; Rüdiger Wanke; Eckhard Wolf; Georg J Arnold Journal: Sci Rep Date: 2016-09-16 Impact factor: 4.379
Authors: Sandra Murphy; Paul Dowling; Margit Zweyer; Michael Henry; Paula Meleady; Rustam R Mundegar; Dieter Swandulla; Kay Ohlendieck Journal: Int J Mol Med Date: 2017-04-18 Impact factor: 4.101
Authors: Pietro Spitali; Kristina Hettne; Roula Tsonaka; Mohammed Charrout; Janneke van den Bergen; Zaïda Koeks; Hermien E Kan; Melissa T Hooijmans; Andreas Roos; Volker Straub; Francesco Muntoni; Cristina Al-Khalili-Szigyarto; Marleen J A Koel-Simmelink; Charlotte E Teunissen; Hanns Lochmüller; Erik H Niks; Annemieke Aartsma-Rus Journal: J Cachexia Sarcopenia Muscle Date: 2018-04-16 Impact factor: 12.910
Authors: Mojgan Reza; Daniel Cox; Lauren Phillips; Diana Johnson; Vaishnavi Manoharan; Michael Grieves; Becky Davis; Andreas Roos; Jennifer Morgan; Michael G Hanna; Francesco Muntoni; Hanns Lochmüller Journal: Neuromuscul Disord Date: 2017-07-10 Impact factor: 4.296