Academisch Ziekenhuis Leiden (Leiden University Medical Center (LUMC)

Leiden University Medical Center (LUMC) is one of the major medical centres in the Netherlands funded by the Dutch Government. It employs nearly 7000 people. The centre is committed to the advancement of health care and education in line with the latest international insights and standards.  LUMC is one of the few academic medical centers in the Netherlands where core activities include fundamental research. Its unique research practice, ranging from pure fundamental medical research to applied clinical research, places LUMC among the world top. This enables LUMC to offer patient care and education in line with the latest international insights and standards.

LUMC offers state-of-the-art research facilities to contribute to innovation scientific research, e.g. Leiden Genome Technology Center, Bioinformatics, Data Analytics, Central Animal and Transgenic Facility, Preclinical Imaging Facility, the C.J. Gorter center for high field MRI, and Biobank Facility. LUMC has a vast experience in EU projects including the FP7 projects BIOIMAGE-NMD, SCOPE-DMD, Bio-NMD, TREAT-NMD, Neuromics and RD-Connect. LUMC also participated in COST Actions BM1208 (Chair), BM1304 (Working Group leader) and CA13107 (Vice-Chair). Furthermore, LUMC participates in 7 ERNs (1 as coordinator) and it is active in 107 granted Horizon2020 projects (35 as coordinator). LUMC researchers participate(d) in 20 IMI projects and LUMC is/has been host institution of 21 European Research Council (ERC) grants. Thus, LUMC has ample experience with the legal and financial administration of European research projects.

The multi-disciplinary team from the LUMC that participates in this proposal will bring a wide range of technical and scientific value to this project as a partner. Due to the involvement of three different departments, Human Genetics, Radiology and Neurology, the pre-clinical, imaging, transcriptomics and clinical aspects of the project are covered. The three departments have a long-standing and successful collaboration for at least 15 years, with more than 10 shared PhD students and a large number of shared publications. The LUMC hosts the national Dutch Dystrophinopathy Database, hosting clinical and genetic information of >500 DMD and BMD patients. LUMC is leading partner in the Duchenne Centre Netherlands, a collaboration between three academical partners and the two patient representative organizations in the Netherlands, which coordinates research and clinical care in the Netherlands. LUMC is also leading the national biobank for DMD and BMD in the Netherlands. Annemieke Aartsma-Rus is the top-rated expert on Duchenne muscular dystrophy on expertscape.com, while the LUMC as center is ranked fifth of the world.

Team

Hermien E. Kan

Dr. H.E. Kan

Position in Organisation
Associate professor

Profile
Dr. Hermien E. Kan is appointed as an Associate Professor of Radiology at the C.J. Gorter Center for High Field MRI of the Department of Radiology at the LUMC in Leiden, The Netherlands and chair of the muscle imaging group at the LUMC. The objectives of her research program are to develop and apply quantitative magnetic resonance methods to study skeletal muscle physiology and disease. She specializes in the application of magnetic resonance imaging and spectroscopy in skeletal muscle and brain. Her group developed and applied quantitative muscle MRI in Duchenne muscular dystrophy (DMD). She translated this approach to Becker MD patients, which is important for outcome measures in clinical trials, and developed methodology at the high-field 7 tesla system for use in patient populations.

Role in the project
Hermien Kan will be the site PI for the LUMC and will be the responsible contact person and member of the steering committee of the project. She will take responsibility for the cooperation and output produced by the LUMC. She will take part in project meetings and present project output at those meetings and scientific events. She will co-supervise the scientific personnel appointed on the project related to the clinical MRI and make an analysis plan for the MR spectroscopy data generated in the project.

Annemieke Aartsma-Rus

Prof Dr. A. Aartsma-Rus

Position in Organisation
Professor of translational genetics

Profile
Prof. Dr. Annemieke Aartsma-Rus is a professor of Translational Genetics. She is one of the pioneers of the antisense-mediated exon skipping therapy for DMD. She is President of the Oligonucleotide Therapeutics Society (2019-2020), Chair of the TREAT-NMD Executive Committee and vice-chair of COST Action CA17103 (Delivery of antisense RNA therapies). In 2015, 2016, 2017, 2018 and 2019 she was selected as most influential scientist in Duchenne muscular dystrophy in the past 10 years by Expertscape. She has published over 190 peer-reviewed papers and 11 book chapters, as well as 15 patents and has edited one book. In 2011 she received the Duchenne Award from the Dutch Duchenne Parent Project in recognition of this work and her dedication to the Duchenne field. In 2020 she received the Black Pearl Science Award for her work educating patient representatives in the rare disease space.

Role in the project
Prof. Aartsma-Rus will be involved in the preclinical WPs (2-4) where she will use her expertise in design of antisense oligonucleotides, performing preclinical studies, the genetics of dystrophin and expertise in dystrophin isoforms, and the analysis of dystrophin to test and optimize antisense oligonucleotides to ensure experimental settings are optimal.

Pietro Spitali

Dr. Pietro Spitali

Position in Organisation
Assistant professor

Profile
Dr. Spitali works at the Human Genetics Department. The focus of his research is to investigate non-invasive tools to monitor the health status of patients affected by neuromuscular disorders. He performed studies in animal models and patients to identify and validate blood biomarkers and genetic modifiers. He has established national and international collaborations with academic and industrial partners. He led the biomarker work in 2 EU funded projects (SCOPE-DMD and NEUROMICS). He obtained funding from charities and industry to explore and develop new wet and dry lab methods. His group is now among the major players in Europe and world-wide for biomarker research in neuromuscular disorders.

Role in the project
Dr. Spitali is WP7 leader. He will supervise the data integration across WPs in order to understand the connection between molecular data (mutation site, dystrophin isoforms binders), histological findings (isoforms localization in brain areas), MRI/MRS and phenotype.

Maaike van Putten

Dr. Maaike van Putten

Position in Organisation
Senior Researcher

Profile
Dr. Maaike van Putten is a senior researcher at the department of Human Genetics of the LUMC. She is specialized in investigating dystrophic animal models. Her research focusses on studying muscle and brain function and pathology in Duchenne mouse models. She aims to improve pathology and functionality through interventions utilizing, amongst others, antisense oligonucleotides.

Role in the project
Dr. van Putten will be responsible for the preclinical work of WPs 2, 3, 4, 6 and 7. She will co-design, execute and co-supervise the projects and appointed scientific personnel. These projects encompass the transcriptomic analyses, behavioural and drug intervention studies, preclinical MRI studies and data integration across the WPs.

Erik H. Niks

Dr. Erik H. Niks

Position in Organisation
Associate professor – Senior medical specialist

Profile
Dr. Erik Niks is consultant neurologist and paediatric neurologist at the department of Neurology at the LUMC, the Dutch Expert Center for Duchenne and Becker Muscular Dystrophies and Acquired Neuromuscular Junction Diseases. In this position he coordinates the multidisciplinary care for children with neuromuscular conditions, in particularly DMD and BMD. Dr. Niks is board member of the Duchenne Centre Netherlands, a national collaboration between three academical partners and the two patient representative organisations, and coordinates the nationwide Dutch Dystrophinopathy Database and, the national biobank for DMD and BMD in the Netherlands facilitated by the Parelsnoer Insitute (https://parelsnoer.org/page/en/Pearls). Since 2008, Dr. Niks has been responsible for the clinical data from LUMC in the biomarker research has worked as principal investigator for clinical trials in DMD and BMD conducted at the LUMC

Role in the project
Dr. Niks will be involved in WPs 5 and 6 in which patients with DMD and BMD will be included. He will be supervising the recruitment of patients in the Netherlands, be responsible for the clinical phenotyping and will co-supervise the scientific personnel appointed on the project related to the clinical MRI and neuropsychological assessments.

Louise van der Weerd

Dr. Louise van der Weerd

Position in Organisation
Associate Professor, pre-clinical imaging

Profile
The research group of Dr. Louise van der Weerd focusses on the use and development of novel MRI and other pre-clinical imaging techniques to characterize neurological and cardiovascular disease processes. The lab is integrated within the departments of Radiology and Human Genetics, securing a smooth integration of the imaging work with pathophysiological validation on animal and cell models. This research is closely linked to parallel research lines in patient research, and to neuropathological research with collaborators in LUMC and at the Netherlands Brain Bank.  Dr. Van der Weerd is a partner or WP leader in several national and European consortia focusing on imaging in neurodegeneration and neurovascular function in general. She also was awarded prestigious personal awards (VENI, VIDI, Athena personal career grant) on this topic.

Role in the project
Dr. Van der Weerd will be involved in WP 6, where she will supervise the pre-clinical imaging activities involving protocol development and optimisation, standardisation and image processing.