Arnold J.J. Reuser – EMC – Erasmus MC, Rotterdam, The Netherlands

arnoldjjreuserInstitute description
The Erasmus Medical Center (EMC), Rotterdam is the largest University Medical Center in the Netherlands and is organized in accordance with public law of the Netherlands. It is an integrated academic medical centre for patient care, research and teaching. It has top-level facilities, medical staff and other personnel to perform these tasks.

The Erasmus Medical Center has held a strong position in the field of lysosomal diseases for more than 30 years and is now considered a leading institution for LSDs in Europe. EMC has achieved crucial milestones in the study of Pompe disease and its know-how and expertise are crucial for the development of WP1 and WP2.
Currently, EMC cares for more than 60 patients with lysosomal diseases (Pompe, MPS I, II and VI), and was leader in the development of enzyme therapy for Pompe disease (proof of principle, 1984; cloning the GAA gene, 1988; knockout mice, 1998; production of recombinant human GAA, 1995/98; first clinical trials,1999; approval, 2006). EMC moderates the Pompe disease mutation database, collects patient information world-wide via patient organizations (IPA) and designs clinical protocols since 2000.

Group leader
Arnold J.J. Reuser, PhD, is Associate Professor of Cell Biology/Histology at the Erasmus Medical Center and member of several advisory boards. He has been studying various aspects of lysosomal diseases (molecular aspects, genotype-phenotype correlation, mutation database, muscle pathology, mouse models, and therapy) since 1973, with a particular attention to Pompe disease. Prof. Reuser has received important awards for his work.

Role in the project
Several EMC Departments (Pediatrics, Clinical Genetics, Internal Medicine, Neurology, Physiotherapy, Cardiology, Bio-informatics and Hospital Pharmacy) are involved in this project (WP1, WP2, WP3).
EMC figures as Workpackage leader for WP2. Tasks in WP1 concern collection and evaluation of muscle biopsy specimens, application of enzyme and DNA/RNA-based analytical procedures including micro-array analyses, cell culture technology, immunocytochemistry, maintenance of the Pompe disease mutation database and the clinical database. Tasks in WP2 concern clinical studies and protocol design for clinical evaluation of children and adults with Pompe disease and MPS VI: a demanding multidisciplinary challenge.

Key personnel

Name Title Gender Role/Expertise
Arnold J.J. Reuser Group leader M WPL for WP2
Ans T. Van der Ploeg Investigator F Clinical heterogeneity in Pompe disease, enzyme therapy
Pieter van Doorn Investigator M Immuno-mediated and neuromuscular disorders, Pompe disease
Marloes Hegemans PhD F Natural course of Pompe disease, patient survey
Marian Kroos MSc F Pompe disease and other LSDs

Key publications

Okumiya T, Kroos MA, Vliet LV, Takeuchi H, Van der Ploeg AT, Reuser AJ (2007). Chemical chaperones improve transport and enhance stability of mutant alphaglucosidases in glycogen storage disease type II. Mol Genet Metabol 90: 49-57.

Hagemans ML, Winkel LP, Hop WC, Reuser AJ, Van Doorn PA, Van der Ploeg AT (2005). Disease severity in children and adults with Pompe disease related to age and disease duration. Neurology 64: 2139-2141.

Van den Hout JM, Kamphoven JH, Winkel LP, Arts WF, De Klerk JB, Loonen MC, Vulto AG, Cromme-Dijkhuis A, Weisglas-Kuperus N, Hop W, Van Hirtum H, Van Diggelen OP, Boer M, Kroos MA, Van Doorn PA, Van der Voort E, Sibbles B, Van Corven EJ, Brakenhoff JP, Van Hove J, Smeitink JA, de Jong G, Reuser AJ, Van der Ploeg AT (2004). Long-term intravenous treatment of Pompe disease with recombinant human alpha-glucosidase from milk. Pediatrics 113: e448-457.

Hermans MM, van Leenen D, Kroos MA, Beesley CE, Van Der Ploeg AT, Sakuraba H, Wevers R, Kleijer W, Michelakakis H, Kirk EP, Fletcher J, Bosshard N, Basel-Vanagaite L, Besley G, Reuser AJ (2004). Twenty-two novel mutations in the lysosomal alpha-glucosidase gene (GAA) underscore the genotype-phenotype correlation in glycogen storage disease type II. Hum Mutat 23: 47-56.

Van den Hout H, Reuser AJ, Vulto AG, Loonen MC, Cromme-Dijkhuis A, Van der Ploeg AT (2000). Recombinant human alpha-glucosidase from rabbit milk in Pompe patients. Lancet 356: 397-398.