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

Landfeldt, E, Lochmüller, H, Lindgren, P. Incomplete description of the current body of evidence of the health economics of Duchenne muscular dystrophy. Orphanet J Rare Dis. 2019.14 (1)75 PMID:30940156

Coenen-Stass, AML, Sork, H, Gatto, S, Godfrey, C, Bhomra, A, Krjutškov, K et al.. Comprehensive RNA-Sequencing Analysis in Serum and Muscle Reveals Novel Small RNA Signatures with Biomarker Potential for DMD. Mol Ther Nucleic Acids. 2018.13 1-15 PMID:30219269

Landfeldt, E, Edström, J, Buccella, F, Kirschner, J, Lochmüller, H. Duchenne muscular dystrophy and caregiver burden: a systematic review. Dev Med Child Neurol. 2018.60 (10)987-996 PMID:29904912

Crow, RA, Hart, KA, McDermott, MP, Tawil, R, Martens, WB, Herr, BE et al.. A checklist for clinical trials in rare disease: obstacles and anticipatory actions-lessons learned from the FOR-DMD trial. Trials. 2018.19 (1)291 PMID:29793540

Spitali, P, Hettne, K, Tsonaka, R, Charrout, M, van den Bergen, J, Koeks, Z et al.. Tracking disease progression non-invasively in Duchenne and Becker muscular dystrophies. J Cachexia Sarcopenia Muscle. 2018.9 (4)715-726 PMID:29682908

Landfeldt, E, Mayhew, A, Straub, V, Lochmüller, H, Bushby, K, Lindgren, P et al.. Psychometric analysis of the pediatric quality of life inventory 3.0 neuromuscular module administered to patients with duchenne muscular dystrophy: A rasch analysis. Muscle Nerve. 2018.58 (3)367-373 PMID:29466827

Willmann, R, Buccella, F, De Luca, A, Grounds, MD, 227th ENMC workshop study group. 227th ENMC International Workshop:: Finalizing a plan to guarantee quality in translational research for neuromuscular diseases Heemskerk, Netherlands, 10-11 February 2017. Neuromuscul. Disord. 2018.28 (2)185-192 PMID:29361397

Lourbakos, A, Yau, N, de Bruijn, P, Hiller, M, Kozaczynska, K, Jean-Baptiste, R et al.. Evaluation of serum MMP-9 as predictive biomarker for antisense therapy in Duchenne. Sci Rep. 2017.7 (1)17888 PMID:29263366

Landfeldt, E, Mayhew, A, Straub, V, Bushby, K, Lochmüller, H, Lindgren, P et al.. Psychometric properties of the Zarit Caregiver Burden Interview administered to caregivers to patients with Duchenne muscular dystrophy: a Rasch analysis. Disabil Rehabil. 2019.41 (8)966-973 PMID:29254382

Koeks, Z, Bladen, CL, Salgado, D, van Zwet, E, Pogoryelova, O, McMacken, G et al.. Clinical Outcomes in Duchenne Muscular Dystrophy: A Study of 5345 Patients from the TREAT-NMD DMD Global Database. J Neuromuscul Dis. .4 (4)293-306 PMID:29125504

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