Neuromuscular Diseases in Children and Adolescents

Neuromuscular Diseases in Children and Adolescents2020-09-15T09:25:45+02:00

Project Description

Dr. Astrid Pechmann

Physician
E: astrid.pechmann@uniklinik-freiburg.de
P: +49 761 270 44977

Department of Neuropediatrics and Muscle Disorders
Center for Pediatrics and Adolescent Medicine
Mathildenstraße 1
79106 Freiburg
Germany

The group’s focus is on translational and clinical research in various neuromuscular diseases.

This involves basic research, diagnostic studies, and setup and organization of patient registries. Special topics of research include genomics, data sharing, gene discovery, collection of real-world data, and participation in several ongoing pharmaceutical clinical trials.

TEAM

  • Dr. Astrid Pechmann, group-leader and physician working on clinical variety and systematic evaluation of spinal muscular atrophies (SMA); co-founder of the SMArtCARE-registry
  • Dr. David Schorling, physician working on clinical biomarkers in neuromuscular diseases, especially in Duchenne muscular dystrophy (DMD) and spinal muscular atrophies (SMA)
  • PD Dr. Hanns Lochmüller, associate physician and scientist; Senior Scientist at the Children’s Hospital of Eastern Ontario (CHEO) Research Institute.
  • PD Dr. Thorsten Langer, physician working on health services research, focused on but not limited to neuromuscular diseases.
  • Dr. Sabine Borell, physician and investigator in several ongoing clinical trials
  • Dr. Matthias Eckenweiler, physician and investigator in several ongoing clinical trials
  • Sabine Wider, study nurse
  • Inka Lotz, study nurse
  • Sabine Stein, physiotherapist; trainer in regular SMArtCARE workshops (physiotherapeutic assessment of SMA patients)
  • Sibylle Vogt, physiotherapist; trainer in regular SMArtCARE workshops (physiotherapeutic assessment of SMA patients)

RESEARCH THEMES

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.

European collaborations

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).

CURRENT RESEARCH PROJECTS

  • 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.

SELECTED RECENT PUBLICATIONS

  • Nusinersen in adults with 5q spinal muscular atrophy: a non-interventional, multicentre, observational cohort study. Hagenacker T, Wurster CD, Günther R, Schreiber-Katz O, Osmanovic A, Petri S, Weiler M, Ziegler A, Kuttler J, Koch JC, Schneider I, Wunderlich G, Schloss N, Lehmann HC, Cordts I, Deschauer M, Lingor P, Kamm C, Stolte B, Pietruck L, Totzeck A, Kizina K, Mönninghoff C, von Velsen O, Ose C, Reichmann H, Forsting M, Pechmann A, Kirschner J, Ludolph AC, Hermann A, Kleinschnitz C. Lancet Neurol. 2020 Apr;19(4):317-325. DOI: 10.1016/S1474-4422(20)30037-5
  • MACF1 links Rapsyn to microtubule- and actin-binding proteins to maintain neuromuscular synapses. Oury J, Liu Y, Töpf A, Todorovic S, Hoedt E, Preethish-Kumar V, Neubert TA, Lin W, Lochmüller H, Burden SJ. J Cell Biol. 2019 May 6;218(5):1686-1705. DOI:10.1083/jcb.201810023
  • Cognitive behavioural therapy with optional graded exercise therapy in patients with severe fatigue with myotonic dystrophy type 1: a multicentre, single-blind, randomised trial. Okkersen K, Jimenez-Moreno C, Wenninger S, Daidj F, Glennon J, Cumming S, Littleford R, Monckton DG, Lochmüller H, Catt M, Faber CG, Hapca A, Donnan PT, Gorman G, Bassez G, Schoser B, Knoop H, Treweek S, van Engelen BGM; OPTIMISTIC consortium. Lancet Neurol. 2018 Aug;17(8):671-680. DOI:10.1016/S1474-4422(18)30203-5
  • Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy. Mercuri E, Darras BT, Chiriboga CA, Day JW, Campbell C, Connolly AM, Iannaccone ST, Kirschner J, Kuntz NL, Saito K, Shieh PB, Tulinius M, Mazzone ES, Montes J, Bishop KM, Yang Q, Foster R, Gheuens S, Bennett CF, Farwell W, Schneider E, De Vivo DC, Finkel RS; CHERISH Study Group. N Engl J Med. 2018 Feb 15;378(7):625-635. DOI: 10.1056/NEJMoa1710504.
  • Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy. Finkel RS, Mercuri E, Darras BT, Connolly AM, Kuntz NL, Kirschner J, Chiriboga CA, Saito K, Servais L, Tizzano E, Topaloglu H, Tulinius M, Montes J, Glanzman AM, Bishop K, Zhong ZJ, Gheuens S, Bennett CF, Schneider E, Farwell W, De Vivo DC; ENDEAR Study Group. N Engl J Med. 2017 Nov 2;377(18):1723-1732. DOI: 10.1056/NEJMoa1702752.

COLLABORATIONS, CO-OPERATIONS AND NETWORKS

  • Prof. Dr. Janbernd Kirschner, Head of Department of Neuropediatrics, Bonn University Hospital, Germany. Professor Kirschner led the Neuromuscular Disorders group at the Freiburg Center for Pediatrics and Adolescent Medicine until April 2019.
  • 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.

FUNDING

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.

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