Citations 3
A randomized, double-blind, placebo-controlled study of losmapimod in patients with facioscapulohumeral muscular dystrophy: Results of the REACH study
Voermans, Nicol C, Statland, J., Hayward, Lawrence J. , Rosenbohm, Angela , Munain, Adolfo López de, Sacconi, Sabrina, Leung, D., Vissing, John, Schoser, Benedikt, Lochmüller, H., Bugiardini, E., Wang, Leo H. , Maggi, Lorenzo, Ragole, Thomas , Pestronk, Alan , Hamel, Johanna , Goyal, Namita A, Korngut, Lawrence, Naddaf, Elie, Harper, A., Shieh, Perry, Kornblum, Cornelia , Sansone, Valeria, Genge, A., Tasca, G., Jiang, John , Jouvin, Marie‐Hélène , Tawil, Rabi , Investigators, on behalf of the REACH, Leung, Doris G , Muelas, Nuria , Wang, Leo H , Pestronk, Alan , Goyal, Namita A , Harper, Amy , Tasca, Giorgio , Tawil, Rabi , Voermans, Nicol Cornelia , Statland, Jeffrey M., Munaín, Adolfo López de , Sacconi, Sabrina , Badrising, Umesh A. , Vissing, John , Schoser, Benedikt , Bugiardini, Enrico , Maggi, Lorenzo , Korngut, Lawrence , Naddaf, Elie , Shieh, Perry B. , Sansone, Valeria , Genge, Angela
Journal of Neuromuscular Diseases | February 6, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Background: Losmapimod is an orally administered small molecule and selective p38α/β mitogen-activated protein kinase (MAPK) inhibitor able to reduce aberrant expression of DUX4 in vitro and thereby potentially slowing disease progression in patients with facioscapulohumeral muscular dystrophy (FSHD). Objective: This global, randomized, placebo-controlled, double-blind phase 3 study in patients with FSHD1 and FSHD2 examined the efficacy and safety of losmapimod over a 48-week treatment period compared to placebo (NCT05397470, EUDRACT 2022-000389-16). Methods: The primary endpoint was change in quantification of reachable workspace (RWS) expressed as relative surface area (RSA). Other endpoints included measures of muscle composition (fat content and lean muscle) using magnetic resonance imaging (MRI), muscle strength using quantitative dynamometry, and quality of life measures. Results: 130 participants received losmapimod and 130 participants received placebo, with 252 participants completing the 48-week treatment period. There were no statistically significant differences between groups in change in RSA and all secondary efficacy endpoints from baseline to Week 48. Losmapimod treatment was well-tolerated, and most adverse events were mild. Conclusions: Losmapimod was generally well tolerated with a favorable safety profile at a dose of 15 mg twice daily. Although none of the efficacy endpoints were met, study design and data from the study may inform future studies of FSHD therapies.
Aktualisierung des Modells pathogener CNBP Repeatexpansionen ursächlich für die Myotone Dystrophie Typ 2
Erdmann, H., Wendlandt, Martin , Rost, Simone , Sauer, Mayra , Golibrzuch, M, Timmer, Manuela , Bier, August, Wunderlich, Gilbert , Walter, Maggie C. , Neuhann, Teresa , Holinski‐Feder, Elke , Abicht, Angela, Erdmann, H, Lucas, Morghan C. , Cordts, Isabell , Kleefeld, Felix , Bier, A, Becker, Kerstin , Kleinle, Stephanie , Wenninger, Stephan , Schoser, Benedikt
Nervenheilkunde | March 11, 2025 | Volume: 44 | Issue: No issue available | Pages: No page available
Polyglucosan body myopathy caused by defective ubiquitin ligase RBCK1
Schoser, Benedikt , Laforêt, Pascal , Kalev, Ognian, Lindberg, Christopher , Romero, Norma B., López, Marcela Dávila , Akman, Hasan O. , Wahbi, Karim , Iglseder, Stephan, Eggers, Christian , Engel, Andrew G. , DiMauro, Salvatore, Oldfors, Anders , Nilsson, Johanna E.
Annals of Neurology | June 24, 2013 | Volume: 74 | Issue: 6 | Pages: 914-919
Glycogen storage diseases are important causes of myopathy and cardiomyopathy. We describe 10 patients from 8 families with childhood or juvenile onset of myopathy, 8 of whom also had rapidly progressive cardiomyopathy, requiring heart transplant in 4. The patients were homozygous or compound heterozygous for missense or truncating mutations in RBCK1, which encodes for a ubiquitin ligase, and had extensive polyglucosan accumulation in skeletal muscle and in the heart in cases of cardiomyopathy. We conclude that RBCK1 deficiency is a frequent cause of polyglucosan storage myopathy associated with progressive muscle weakness and cardiomyopathy. Ann Neurol 2013;74:914–919