Header AG Spuler

Spuler Lab



We take our muscles for granted. They permit us to go about our daily lives and with perhaps the exception of a few aches and pains they serve us well until our lives have ended.

However, for persons with genetic muscle diseases, this happy state-of-affairs is not the case.

These persons are wheel chair bound from child- or young adulthood until they die. There are many such patients. Genetic muscle diseases are not rare. But acquired muscle diseases such as critical care myopathy, muscle cachexia following cancer, heart failure or renal failure, traumatic muscle ischemia, or myopathy following drug reactions are definitely even more common.

We still have no treatment for any genetic muscle disease. However, we have made marked progress on an understanding of their pathologies. For acquired muscle disease, we are in the process of developing treatment strategies, although as always, “vigilance equals avoidance”.

Out-patient Clinic for Muscle Diseases


Group Leader

Prof. Dr. Simone Spuler



Phone +49 30 450540501 and 450540504


Administrative Coordinator

Susanne Wissler




Phone +49 30 450540504

Administrative Coordinator of the Research Group "Muscle Sciences and University Outpatient Clinic for Muscle Disorders" and the International Research Training Group for Myology (MyoGrad) since 2010


Senior Scientist

Dr. Andreas Marg



Phone +49 30 450540518

Postdoctoral fellow since 2011 and senior scientist of the group

Involved in the project “Human muscle stem cells as an Advanced Therapy Medicinal Product (ATMP)”




Dr. Helena Escobar Fernandez



Phone +49 30 450540518

MyoGrad PhD fellowship from 2011-2015 and postdoctoral fellow since 2016

Involved in the project “Precise gene editing of muscular dystrophy-causing mutations in patient-derived induced pluripotent stem cells”


Dr. Stefanie Grunwald



Phone +49 30 450540519

Postdoctoral fellow since 2010

Involved in the project „Impact of statin-induced myopathy on human muscle“


Dr. Joanna Schneider



Phone +49 30 450540514

­Research fellow and physician in the outpatient clinic for muscular disorders 2004-2013

Fellow of the Clinician Scientist Program of the Charité and MDC since 2016

Involved in the project “Epigenetic changes in critical illness myopathy”



Dr. Stefanie Seelk



Phone +49 30 450540518


Elisabetta Gazzerro


Phone +49 30 450540514

Clinician scientist and responsible for the outpatient clinic for muscular disorders

Involved in the project “Immunological impact of muscular dystrophies”


Janine Kieshauer, M. Sc.



Phone +49 30 450540518


PhD students

Silvia Di Francescantonio, M. Sc. Medical Biology



Phone +49 30 450540514

PhD student (MyoGrad PhD fellowship) since January 2017

Involved in the project “Developing of a human muscle stem cell culture strategy to investigate the maintenance of stem cell quiescence”


Henning Langer, M. Sc. Human Biology



Phone +49 30 450540518

PhD student (MyoGrad PhD fellowship and additionally member of the BCRT) 

Involved in the project “The regulation of skeletal muscle metabolism in health and disease”


Jakub Malcher, M. Sc. Biotechnology



Phone +49 30 450540518

PhD student (MyoGrad PhD fellowship)

Involved in the project “Exon skipping and genome editing as therapeutic strategies in dysferlinopathy”


Eric Metzler, M. Sc. Technical Biology



Phone +49 30 450540518

Involved in the project “Primary and induced pluripotent stem cell-derived human satellite cells for cell-based therapies”


Technical Assistents

Stephanie Meyer-Liesener (Head Technician)



Phone +49 30 450540506


Stefanie Haafke


Phone +49 30 450540518


Adrienne Rothe



Phone +49 30 450540518


Andrea Behm


Phone +49 30 450540518


Eyad Al Emam



Phone +49 30 450540518



Gene Editing in Muscular Dystrophies

Involved people: Helena Escobar, Jakub Malcher

Precise gene editing of muscular dystrophy-causing mutations in patient-derived induced pluripotent stem cells

Helena Escobar, PhD

Muscular dystrophies are devastating diseases for which specific treatments are still lacking. They cause a progressive loss, degeneration and weakness of skeletal muscle and are often monogenic (caused by mutations in a single gene). A possible therapeutic avenue is thus to repair the genetic defect in patient-derived cells and later use those for autologous transplantation. Muscle stem cells (MSC) are responsible for muscle regeneration and would be the cell type of choice for repairing dystrophic muscles in a cell therapy context. However, they are scarce within the muscle tissue, have a limited proliferative potential and are difficult to manipulate genetically. Therefore, the number of MSC that could be taken from a patient and re-infused following gene repair would likely not suffice to treat large groups of muscles. Induced pluripotent stem cells (iPSC), on the other hand, can be generated from the patient’s adult somatic cells, widely expanded ex vivo, genetically corrected and differentiated back into cells displaying some of the characteristics of MSC. Our work focuses on developing a platform for precise gene editing of muscular dystrophy-causing mutations in patient-derived iPSC and the subsequent generation of gene-corrected MSC-like cells from each individual donor. We are developing methods to reliably assess the phenotypic rescue of the genetic defect in vitro as well as the biosafety features and in vivo regenerative potential of the gene-corrected iPSC-derived MSC through transplantation studies into mouse skeletal muscle.

Exon skipping and genome editing as therapeutic strategies in dysferlinopathy

Jakub Malcher, M.Sc. Biotechnology

Limb-girdle muscular dystrophy type 2B (LGMD2B) is characterised by progressive muscle wasting that starts manifesting in young adults and progresses throughout their whole life. It is caused by mutations in the dysferlin gene that lead to the formation of misfolded dysferlin proteins affecting the muscle repair process. Using a new knock-in mouse carrying a missense mutation in one of the exons, gene therapy strategies including exon skipping and genome editing are studied. The project aim is to design appropriate antisense sequences that will be capable of removing the exon of interest and form a truncated but functional version of dysferlin. The feasibility of exon skipping is assessed using an in vitro model and the laser wounding assay. We are investigating the therapeutic efficacy both in vitro and in vivo. During the project, we also study possibilities of permanent mutation repair by means of currently available genome editing techniques.

Muscle Stem Cells

Involved people: Andreas Marg, Janine Kieshauer, Silvia Di Francescantonio, Eric Metzler

Satellite cells and heterogeneity

Andreas Marg, PhD

Muscle repair and regeneration require activation of satellite cells. These rare muscle precursor cells are located in a specific niche and are probably mitotically quiescent in healthy muscle. It is unclear to what extent satellite cells are heterogeneous in respect to their gene expression profiles, their myogenic differentiation potential and their stemness. Today, our understanding of human satellite cell heterogeneity is fragmentary, but clinical applications of stem cell populations require extensive knowledge in this field.

In collaboration with the Berlin Institute for Medical Systems Biology (BIMSB), we use Drop-seq, a method that allows profiling of thousands of single cells by separating them in tiny droplets with barcoded primer beads. After sequencing, we get the mRNA expression profiles from thousands of satellite cells. This is a significant step for a better understanding of these fascinating cells.

Reprogramming and redifferentiation of human muscle stem cells into induced pluripotent stem cells

Eric Metzler, M.Sc. Technical Biology

The development of cell-based therapies represents a keystone in the research aiming for the treatment of muscular dystrophies. Therefore, one part of this work aims to develop promising culture techniques for primary human biopsy-derived satellite cells to improve the outcome of engraftment experiments.

Unfortunately, primary satellite cells will hardly become available in the required high numbers. Instead, human induced pluripotent stem cells (iPSCs) represent the key to unrestricted cell numbers necessary for gene correction and repopulation of large muscles for therapeutic purposes without evoking an immune response. Thus, another major part of this work aims to establish the differentiation of human iPSCs towards the myogenic lineage by recently published protocols.

Toxic Myopathies

Involved people: Joanna Schneider, Stefanie Grunwald

The impact of statins on human muscle

Stefanie Grunwald, PhD

Statins are effective cholesterol reducing drugs and are prescribed to millions worldwide. They inhibit HMG-CoA-reductase, a key enzyme of the cholesterol synthesis. Lowering blood cholesterol levels reduces the risk to develop cardiovascular diseases. But why can statin treatment become a problem for patients?

About 10-15% of patients develop muscle-related side effects while ingesting statins – statin-induced myopathy (StiM). This can include an increase in creatine kinase blood levels, muscle pain (myalgia), and very rare muscle breakdown (rhabdomyolysis).

In our study, we combine an investigator-initiated observational clinical study and a translational research study investigating the effect of statins on human muscle. For our clinical study, we recruit statin-treated patients with and without muscle-related side effects. We perform laboratory tests and genetic association studies. However, the molecular mechanisms of StiM are unresolved. Changes in cholesterol levels of muscle membranes or effects on muscle cell metabolism may play a role. In the main part of the project we study this question also at cellular level using human muscle cells in culture. We use a wide variety of biochemical, cellular, and biomolecular applications as well as analyses at whole transcriptome (Next Generation Sequencing) and proteome level. For that we studied methods for visualizing and analyzing of OMICs Data. First results indicate that changes in muscle cell metabolism rather than in cholesterol levels are associated with StiM.

Other Projects

Involved people: Henning Langer, Elisabetta Gazzerro

The regulation of skeletal muscle metabolism in health and disease

Henning Langer, M.Sc. Human Biology

Skeletal muscle is the largest organ of the human body. Age- and disease-related loss of muscle mass is associated with severe pathologies. Muscle size and strength are inversely correlated with mortality. Therefore, designing feasible methods to ameliorate muscle size has become a main goal within the field of muscle sciences. With no approved drug available, exercise and nutrition are currently the only clinically relevant bona fide interventions. This project is focusing on the role of energy availability and muscle plasticity. We use models of load-induced hypertrophy and disease-induced atrophy to investigate the regulation of muscle size in a holistic manner. The effect of nutritional interventions to manipulate these processes is evaluated. Changes in size, composition and lean mass of muscles in response to differences in energy intake are monitored. Contemporary GC-MS technology are used to assess changes of the metabolome in muscle, blood and other tissues. This integrative systemic approach enables us to study to which degree phenotypical changes of skeletal muscle are preceded or reflected by changes of the metabolome. The combination of these methods will allow us to broaden the knowledge about strategies to improve muscle health.

Clinical Research

Involved people: Michael Boschmann, Jeanette Schulz-Menger, Elisabetta Gazzerro

  • International clinical trial on the natural history of dysferlinopathies
  • Muscle metabolism in facioscapulohumeral muscular dystrophy
  • Cardiac involvement in facioscapulohumeral muscular dystrophy