The field of neuromuscular diseases encompasses a wide clinical spectrum in terms of etiology, severity and treatment options. We focus on clinical research in spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD) and other rare, mostly genetic neuromuscular diseases.
Recent advances in the field include the identification of many causative genes and the elucidation of the underlying molecular mechanisms. This has opened up new avenues for targeted therapies including gene therapy. The landscape of SMA treatment in particular has changed dramatically over the last years; several novel therapeutic approaches are already available or close to entering routine clinical practice.
Spinal Muscular Atrophy (SMA)
Freiburg has played a major role in the pivotal trials for antisense oligonucleotide based treatments of SMA. Real-world outcome data of SMA patients is collected longitudinally in the Freiburg-based SMArtCARE-project, with currently 50 centers across Germany, Austria and Switzerland contributing data through a state-of-the art platform. Because evidence from previous clinical studies is very limited in this disease, the project aims to evaluate available treatment options across all subtypes and age of patients. This will provide essential information to regulators, payers, clinicians and patients about the long-term impact of these innovative treatments.
Clinical biomarkers in neuromuscular disease
Another focus of the group is work on establishment and validation of clinical biomarkers in neuromuscular disease. The clinical course of most neuromuscular diseases is evaluated and documented by established disease-specific physiotherapeutic scoring systems. However, these scoring systems do not necessarily depict the functional status in daily-life activities and sometimes have a limited inter-rater reliability.
Taking Duchenne Muscular Dystrophy (DMD) as a model-disease, we aim to establish biomarkers that reflect patients’ability to perform daily-life requirements, for example by mechanographic analysis of stair-climbing. Biochemical research on biomarkers is planned in SMA. Systematic examination of biomaterials of SMA patients of all subgroups will be performed in cooperation with the Leibniz-Institute in Dortmund (ISAS) and the neuropediatric department at Essen University Hospital, Germany.
In addition, our group contributes actively to European research and infrastructure projects in rare and neuromuscular diseases, including Solve-RD (Solving the Unsolved Rare Diseases, led by Tübingen University), EJP-RD (European Joint Project for Rare Diseases) and the European Reference Network for Neuromuscular Diseases (EURO-NMD) with associated registries (led by Paris).
- SMArtCARE – Clinical evaluation and monitoring of patients with spinal muscular atrophy (cooperation with Prof. Kirschner, Department of Neuropediatrics, University Hospital Bonn)
- Airwave-oscillometry as complementary pulmonary function testing in children and adolescents (cooperation with AG Pediatric Pneumology; ZKJ Freiburg)
- Analysis of proteom in SMA – searching biomarkers in CSF, blood and urine of patients with spinal muscular atrophy (cooperation with Department of Pediatric Neurology, Essen and ISAS Dortmund)
- NMD-LEONARDO – mechanographic analysis of stair-climbing in DMD
- DMD-Coagulation – Are there abnormalities in hemostasis in patients with duchenne muscular dystrophy?
- Post dural puncture headache in children – retrospective, single-center study prevalence via chart review and questionnaire
The team is involved in several ongoing clinical trials. For a synopsis (in German) of ongoing studies, please visit our section of the ZKJ Study Office webpage here.
Astrid Pechmann is a Fellow in the Berta-Ottenstein Programme for Clinician Scientists (Freiburg University Medical Center)
David Schorling has received a scholarship from the German Society of Neuropediatrics (Gesellschaft für Neuropädiatrie, GNP), 2020.