Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is the most common childhood muscular dystrophy and is caused by defects in the DMD gene, which is responsible for making the protein dystrophin. It is an X-linked disease, which means that it affects almost exclusively boys, and is characterized by progressive muscle degeneration and weakness. Affected individuals have proximal muscle weakness, which causes a waddling gait, toe-walking, lordosis, frequent falls, and difficulty in getting up from the floor and climbing stairs. First symptoms are often evident before 3 years of age, but the disease is often not diagnosed until several years later. Its progressive nature means that most affected boys will start using a wheelchair around the age of 10, although treatments such as steroid therapy can help retain walking ability for longer.

In addition to the vulnerability of skeletal muscle, patients present with weakness of breathing muscles and may have cardiomyopathy, scoliosis and learning difficulties. DMD affects about one in 5,000 males at birth. The DMD gene is the largest known gene in humans and defects in the gene cause the absence of functional dystrophin, a component of the dystrophin-associated glycoprotein complex which anchors the extracellular matrix to the cytoskeleton via F-actin. Dystrophin accumulates at the neuromuscular junction (NMJ) and at a variety of synapses in the peripheral and central nervous systems.

Our group’s DMD-related research focuses on the pathophysiological processes leading to the cardiomyopathy symptoms and the definition of new treatment concepts via the utilization of a new established cardiac in vitro model for the disease. We are also engaged in a variety of projects towards the identification and validation of DMD biomarkers as well as in clinical research.

Hanns is a member of the Scientific Advisory Board of the German Duchenne foundation “Aktion Benni & Co” and in 2016 he was honored with the “Humanpreis” Lifetime Achievement Award for his outstanding commitment to the field of Duchenne research.

 

 

 

 

*Photo with the kind permission of Silvia Hornkamp, Aktion Benni & Co

 

dmd

Relevant publications

Atalaia, A, Wandrei, D, Lalout, N, Thompson, R, Tassoni, A, 't Hoen, PAC et al.. EURO-NMD registry: federated FAIR infrastructure, innovative technologies and concepts of a patient-centred registry for rare neuromuscular disorders. Orphanet J Rare Dis. 2024.19 (1)66 PMID:38355534

Landfeldt, E, Phung, K, Zaman, F, Åström, E, Abner, S, Lochmüller, H et al.. Bisphosphonates in Glucocorticoid-Treated Patients With Duchenne Muscular Dystrophy: A Systematic Review and Grading of the Evidence. Neurology. 2024.102 (2)e207948 PMID:38165327

Landfeldt, E, Aleman, A, Abner, S, Zhang, R, Werner, C, Tomazos, I et al.. Factors Associated with Respiratory Health and Function in Duchenne Muscular Dystrophy: A Systematic Review and Evidence Grading. J Neuromuscul Dis. 2024.11 (1)25-57 PMID:37980679

McMillan, HJ, Lochmüller, H. Sustained clinical benefit following systemic gene replacement therapy in Duchenne muscular dystrophy. Muscle Nerve. 2024.69 (1)4-6 PMID:37969074

Kekou, K, Svingou, M, Vogiatzakis, N, Nitsa, E, Veltra, D, Marinakis, NM et al.. Retrospective analysis of persistent HyperCKemia with or without muscle weakness in a case series from Greece highlights vast DMD variant heterogeneity. Expert Rev Mol Diagn. 2023.23 (11)999-1010 PMID:37754746

van Cruchten, RTP, van As, D, Glennon, JC, van Engelen, BGM, 't Hoen, PAC, OPTIMISTIC consortium et al.. Clinical improvement of DM1 patients reflected by reversal of disease-induced gene expression in blood. BMC Med. 2022.20 (1)395 PMID:36352383

McMillan, HJ, Lochmüller, H. Biomarkers in Duchenne and Becker muscular dystrophies. Muscle Nerve. 2021.64 (1)4-5 PMID:34076279

Hodgkinson, V, Lounsberry, J, M'Dahoma, S, Russell, A, Jewett, G, Benstead, T et al.. The Canadian Neuromuscular Disease Registry 2010-2019: A Decade of Facilitating Clinical Research Througha Nationwide, Pan-NeuromuscularDisease Registry. J Neuromuscul Dis. 2021.8 (1)53-61 PMID:32925088

Passarelli, C, Selvatici, R, Carrieri, A, Di Raimo, FR, Falzarano, MS, Fortunato, F et al.. Tumor Necrosis Factor Receptor SF10A (TNFRSF10A) SNPs Correlate With Corticosteroid Response in Duchenne Muscular Dystrophy. Front Genet. 2020.11 605 PMID:32719714

Strandberg, K, Ayoglu, B, Roos, A, Reza, M, Niks, E, Signorelli, M et al.. Blood-derived biomarkers correlate with clinical progression in Duchenne muscular dystrophy. J Neuromuscul Dis. 2020.7 (3)231-246 PMID:32390640

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