This research group is co-led by PD Dr. Astrid Pechmann and Prof. Dr. Janbernd Kirschner and focuses on translational and clinical research in the field of rare diseases, with a particular focus on neuromuscular diseases in children and adolescents. The research priorities include innovative diagnostic methods, new, often mutation-specific drug therapies, and the collection of real-world data in the context of registries and databases. The overarching goal is to accelerate the diagnosis of rare diseases and support the development of effective therapies.

• PD Dr. Astrid Pechmann, co-leader of the research group, consultant pediatric neurologist; co-founder of the SMArtCARE-registry, PI in several clinical trials for neuromuscular diseases
• Prof. Dr. Janbernd Kirschner, co-leader of the research group, medical director of the Department of Neuropediatrics and Muscle Disorders, co-founder of the SMArtCARE registry, member of the executive board of EURO-NMD, PI for several research projects and clinical trials
• Prof. Dr. Hanns Lochmüller, associate physician and scientist; Senior Scientist at the Children’s Hospital of Eastern Ontario (CHEO) Research Institute, member of the executive board of EURO-NMD
• Prof Dr. Thorsten Langer, physician working on health services research, focused on but not limited to neuromuscular diseases.
• PD Dr. Nikolai Jung, pediatrician and investigator in several ongoing clinical trials
• Dr. Matthias Eckenweiler, consultant pediatric neurologist and investigator in several ongoing clinical trials
• Sabine Wider, senior study coordinator
• Monika Lisicka, study coordinator
• Jessica Günter, study coordinator
• Katharina Dörnbrack, project manager
• Simone Bürklin, project manager
• Claudia Schmälzle, project manager
• Christine Mauz, project assistant
• Tim Kampowski, data manager
• Franziska Wenzel, data manager
• Sven Seilnacht, data manager
• Sabine Stein, senior physiotherapist; trainer in regular SMArtCARE workshops (physiotherapeutic assessment of SMA patients)
• Sibylle Vogt, senior physiotherapist; trainer in regular SMArtCARE workshops (physiotherapeutic assessment of SMA patients)

Neuromuscular Diseases in Children and Adolescents

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 more than 70 centers across Germany, Austria and Switzerland contributing data through a state-of-the art platform. Because evidence from previous clinical trials is very limited in this disease, the project aims to evaluate available treatment options across all subtypes and ages of patients. Therefore, SMArtCARE will provide essential information to clinicians, regulators, payers, and patients about the long-term impact of these innovative treatments. The German HTA agency, G-BA, has mandated data collection for SMA treatments within the SMArtCARE registry to evaluate their additional benefit.

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.

European collaborations

In addition, our group contributes actively to European research and infrastructure projects in rare and neuromuscular diseases, including ERDERA (European Rare Disease Research Alliance), the European Reference Network for Neuromuscular Diseases (EURO-NMD) with associated registries (led by Paris), and SCREEN4CARE, a EU-funded project to accelerate diagnosis for patients with rare diseases.

• 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

• Solve-RD 

• EJP-RD

• EURO-NMD

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.

• Clinical Effectiveness of Newborn Screening for Spinal Muscular Atrophy: A Nonrandomized Controlled Trial.Schwartz O, Vill K, Pfaffenlehner M, Behrens M, Weiß C, Johannsen J, Friese J, Hahn A, Ziegler A, Illsinger S, Smitka M, von Moers A, Kölbel H, Schreiber G, Kaiser N, Wilichowski E, Flotats-Bastardas M, Husain RA, Baumann M, Köhler C, Trollmann R, Schwerin-Nagel A, Eisenkölbl A, Schimmel M, Fleger M, Kauffmann B, Wiegand G, Baumgartner M, Rauscher C, Cirak S, Gläser D, Bernert G, Hagenacker T, Goldbach S, Probst-Schendzielorz K, Lochmüller H, Müller-Felber W, Schara-Schmidt U, Walter MC, Kirschner J, Pechmann A; SMARTCARE study group. JAMA Pediatr. 2024 Apr 8:e240492. doi: 10.1001/jamapediatrics.2024.0492. Online ahead of print. PMID: 38587854
• EURO-NMD registry: federated FAIR infrastructure, innovative technologies and concepts of a patient-centred registry for rare neuromuscular disorders. Atalaia A, Wandrei D, Lalout N, Thompson R, Tassoni A, ‘t Hoen PAC, Athanasiou D, Baker SA, Sakellariou P, Paliouras G, D’Angelo C, Horvath R, Mancuso M, van der Beek N, Kornblum C, Kirschner J, Pareyson D, Bassez G, Blacas L, Jacoupy M, Eng C, Lamy F, Plançon JP, Haberlova J, Brusse E, Hoeijmakers JGJ, de Visser M, Claeys KG, Paradas C, Toscano A, Silani V, Gyenge M, Reviers E, Hamroun D, Vroom E, Wilkinson MD, Lochmuller H, Evangelista T. Orphanet J Rare Dis. 2024 Feb 14;19(1):66. doi: 10.1186/s13023-024-03059-3. PMID: 38355534
• Effect of nusinersen on motor, respiratory and bulbar function in early-onset spinal muscular atrophy. Pechmann A, Behrens M, Dörnbrack K, Tassoni A, Stein S, Vogt S, Zöller D, Bernert G, Hagenacker T, Schara-Schmidt U, Schwersenz I, Walter MC, Baumann M, Baumgartner M, Deschauer M, Eisenkölbl A, Flotats-Bastardas M, Hahn A, Horber V, Husain RA, Illsinger S, Johannsen J, Köhler C, Kölbel H, Müller M, von Moers A, Schlachter K, Schreiber G, Schwartz O, Smitka M, Steiner E, Stögmann E, Trollmann R, Vill K, Weiß C, Wiegand G, Ziegler A, Lochmüller H, Kirschner J; SMArtCARE study group. Brain. 2023 Feb 13;146(2):668-677. doi: 10.1093/brain/awac252. PMID: 35857854
• Improved upper limb function in non-ambulant children with SMA type 2 and 3 during nusinersen treatment: a prospective 3-years SMArtCARE registry study. Pechmann A, Behrens M, Dörnbrack K, Tassoni A, Wenzel F, Stein S, Vogt S, Zöller D, Bernert G, Hagenacker T, Schara-Schmidt U, Walter MC, Bertsche A, Vill K, Baumann M, Baumgartner M, Cordts I, Eisenkölbl A, Flotats-Bastardas M, Friese J, Günther R, Hahn A, Horber V, Husain RA, Illsinger S, Jahnel J, Johannsen J, Köhler C, Kölbel H, Müller M, von Moers A, Schwerin-Nagel A, Reihle C, Schlachter K, Schreiber G, Schwartz O, Smitka M, Steiner E, Trollmann R, Weiler M, Weiß C, Wiegand G, Wilichowski E, Ziegler A, Lochmüller H, Kirschner J; SMArtCARE study group. Orphanet J Rare Dis. 2022 Oct 23;17(1):384. doi: 10.1186/s13023-022-02547-8. PMID: 36274155 Free PMC article.
• Improvements in Walking Distance during Nusinersen Treatment – A Prospective 3-year SMArtCARE Registry Study. Pechmann A, Behrens M, Dörnbrack K, Tassoni A, Wenzel F, Stein S, Vogt S, Zöller D, Bernert G, Hagenacker T, Schara-Schmidt U, Walter MC, Steinbach M, Blaschek A, Baumann M, Baumgartner M, Becker B, Flotats-Bastardas M, Friese J, Günther R, Hahn A, Küpper H, Johannsen J, Kamm C, Koch JC, Köhler C, Kölbel H, Kolzter K, von Moers A, Naegel S, Neuwirth C, Petri S, Rödiger A, Schimmel M, Schrank B, Schreiber G, Smitka M, Stadler C, Steiner E, Stögmann E, Trollmann R, Türk M, Weiler M, Stoltenburg C, Willichowsky E, Zeller D, Ziegler A, Lochmüller H, Kirschner J; SMArtCARE study group. J Neuromuscul Dis. 2023;10(1):29-40. doi: 10.3233/JND-221600. PMID: 36565133 Free PMC article.
• Mechanographic analysis of the timed 4 stair climb test – methodology and reference data of healthy children and adolescents. Schorling DC, Rawer R, Kuhlmann I, Müller C, Pechmann A, Kirschner J. J Musculoskelet Neuronal Interact. 2023 Mar 1;23(1):4-25. PMID: 36856096 Free PMC article.

• Prof. Dr. univ. Ulrike Schara, Head of Department of Pediatric Neurology, Developmental Neurology and Social Pediatrics, University of Duisburg-Essen, Essen, Germany.
• Heike Kölbel, Department of Pediatric Neurology, Developmental Neurology and Social Pediatrics, University of Duisburg-Essen, Essen, Germany.
• Dr. Andreas Roos, Department of Pediatric Neurology, Developmental Neurology and Social Pediatrics, University of Duisburg-Essen, Essen, Germany and ISAS Dortmund.
• Dr. Sebastian Bode, Department of General Pediatrics and Adolescent Medicine, and Neonatology, Medical Center – University of Freiburg.
• Prof. Dr. Barbara Zieger, Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Medical Center – University of Freiburg.

• SMArtCARE – Clinical evaluation and monitoring of patients with spinal muscular atrophy
• ERDERA – European Rare Disease Research Alliance
• EURO-NMD – European Reference Network for Rare Neuromuscular Diseases
  
• SCREEN4CARE – Shortening  the path to rare disease diagnosis by using newborn genetic screening and digital technologies

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.

Funding sources:

ERDERA, EURO-NMD, and SCREEN4CARE projects are supported by the European Union. The SMArtCARE registry is supported by Biogen, Novartis and Roche.