Repeat Expansions & Myotonic Dystrophy (REDs)

Our research focuses primarily on Myotonic Dystrophy, one of the most frequent neuromuscular diseases in adults. More specifically, our work is mainly concentrated on Myotonic Dystrophy type 1 (DM1), also known as Steinert disease. DM1 is characterised by progressive muscle weakness and atrophy, myotonia, heart conduction defects, cataracts, endocrine and gastrointestinal problems, as well as neurological manifestations. There are five clinical forms of this multisystemic disease, including late-onset, adult, juvenile, infantile and congenital forms. Currently, there is no treatment for this debilitating genetic disorder, but some therapeutic approaches are currently being developed.

DM1 is an autosomal dominant disease caused by the abnormal expansion of a CTG trinucleotide repeat (n>40) located in the 3′ non-coding region of the DMPK gene. The expanded CTG repeat sequence is highly unstable, further increasing in size not only in different tissues throughout the patient’s life, but also between successive generations. The expansion-biased intergenerational instability of the CTG repeat provides the molecular explanation for the anticipation phenomenon typical of this disease. DM1 is an RNA gain-of-function disease. Expanded DMPK transcripts containing pathological CUG repeats (RNA-CUGexp) are retained in the cell nucleus as riboprotein aggregates (foci) and disrupt the function of important RNA binding proteins (RBPs). In particular, RNA foci sequester RBPs of the MBNL family which are involved in RNA processing and maturation. Thus, the functional loss of MBNL activity leads to alternative splicing defects in a subset of RNA transcripts, which have been associated with key disease symptoms: the abnormal splicing of CLCN1 contributes to myotonia, INSR to insulin resistance, BIN1 to muscle weakness, DMD to altered muscle fibre architecture and SCN5A to defects in cardiac conduction and arrhythmias. However, additional mechanisms operating in various tissues and cell types are involved in the complex pathophysiology of this disease.

The REDs research team was created in 2019, following the merge of the teams of Geneviève Gourdon and Denis Furling. It also includes the group of Guillaume Bassez, a neurologist who coordinates the French Myotonic Dystrophy national registry (DM-Scope); and Arnaud Ferry’s group that focuses on muscle physiology and exercise. The aim of this new multidisciplinary team is to synergise efforts in order accelerate translational research for this neuromuscular disease, with the ultimate aim of offering novel and efficient therapeutic alternatives to patients. To this end, our team carries out integrated research on multiple aspects of DM1, from gene mutation to disease symptoms and the development of new therapeutic strategies. Our projects cover the fundamental mechanisms CTG repeat instability, the understanding of the pathophysiological mechanisms of disease using cellular and animal models, the development and assessment of innovative therapeutic approaches and, finally, the setting up of pre-clinical and clinical trials for DM1.

Research topics

Gourdon group

  • Mechanisms of trinucleotide repeat instability in DM1 families, cell and mouse models.
  • Molecular and pathophysiological consequences of CTG expansions in the central nervous system and in the congenital form of the disease.
  • Preclinical therapeutic assays in DM1 mice, through the assessment of molecular and physiological phenotypes in muscle and CNS.

Furling group

  • Pathophysiological mechanisms triggered by the expression of CUGexp-RNA and the resulting changes in the motor unit and muscular function, as well as in other non-muscular manifestations (e.g. cardiovascular…).
  • Development and evaluation of innovative therapeutic approaches for DM1 using cell and mouse models of the disease

Ferry Group

  • Impact of neuromuscular disease on muscle function and performance (i.e., characterisation of mouse models). Effects of exercise.
  • Evaluation of therapeutic approaches on muscle function. Preclinical studies in mouse models, in collaboration with the UMS28 Phenotyping Platform (S. Morosan and M. Lemaitre).
  • Integrated physiology of skeletal muscle.

Bassez group

  • Phenotypic characterisation and natural history of Myotonic Dystrophy.
  • Validation of measurement tools and readouts for clinical trials.
  • Coordination of the French Observatory of Myotonic Dystrophies (DM-Scope).


343 documents

  • Louison Lallemant, Sandra Braz, Anchel González-Barriga, Paul Magneron, Aurélien Cordier, et al.. Toxic CUG RNA repeats disrupt developmentally-regulated splicing in oligodendrocytes causing transient hypomyelination in a mouse model of myotonic dystrophy.. The European Meeting on Glial Cells in Health and Disease, Jul 2023, Berlin, France. ⟨hal-04005524⟩
  • Alex Corscadden, Louison Lallemant, Hélène Benyamine, Jean-Christophe Comte, Aline Huguet-Lachon, et al.. Defects in mouse cortical glutamate uptake can be unveiled in vivo by a two-in-one quantitative microdialysis.. NeuroFrance, May 2023, Lyon, France. ⟨hal-04005564⟩
  • Paul Magneron, Louison Lallemant, Luis Guillermo Correa Parra, Mário Gomes-Pereira, Geneviève Gourdon. Cytoskeleton abnormalities triggered by toxic CUG RNA repeats in DM1 astrocytes.. NeuroFrance, May 2023, Lyon20, France. ⟨hal-04005541⟩
  • B Potier, Louison Lallemant, Sandrine Parrot, Aline Huguet-Lachon, Geneviève Gourdon, et al.. DM1 transgenic mice exhibit abnormal neurotransmitter homeostasis and synaptic plasticity in association with RNA mis-splicing in the hippocampus.. NeuroFrance, May 2023, Lyon, France. ⟨hal-04005556⟩
  • Paul Magneron, Louison Lallemant, Luis Guillermo Correa Parra, Geneviève Gourdon, Mário Gomes-Pereira. Cytoskeleton abnormalities triggered by toxic CUG RNA repeats in DM1 astrocytes.. French Glial Cell Club, May 2023, Lyon, France. ⟨hal-04005531⟩
  • Caroline Le Guiner, Thibaut Larcher, Aude Lafoux, Gilles Toumaniantz, Geneviève Gourdon, et al.. Characterization of the muscular and cardiac diseases of the DMSXL mouse model, a transgenic mouse model for Myotonic Dystrophy type 1. American Society of Gene and Cell Therapy, May 2023, Los Angeles, United States. ⟨hal-04005583⟩
  • Mário Gomes-Pereira. Toxic RNA and glial cell pathology: deciphering brain dysfunction in myotonic dystrophy. 9th Molecular and Cell Biology Symposium, Feb 2023, Porto, Portugal. ⟨hal-04007409⟩
  • Julie Tahraoui-Bories, Antoine Mérien, Anchel González-Barriga, Jeanne Lainé, Céline Leteur, et al.. MBNL‐dependent impaired development within the neuromuscular system in myotonic dystrophy type 1. Neuropathology and Applied Neurobiology, 2023, 49 (1), ⟨10.1111/nan.12876⟩. ⟨hal-03992575⟩
  • Stéphanie Tomé. Long read sequencing in DM1. Workshop on Long read sequencing of expanded tandem repeats, Dec 2022, London, United Kingdom. ⟨hal-04004440⟩
  • Tanya Stojkovic, Marion Masingue, Helène Turmel, Marianne Hezode-Arzel, Anthony Béhin, et al.. Diagnostic yield of a practical electrodiagnostic protocol discriminating between different congenital myasthenic syndromes. Neuromuscular Disorders, 2022, 32 (11-12), pp.870-878. ⟨10.1016/j.nmd.2022.10.001⟩. ⟨hal-03993811⟩

AFM Telethon : innover pour guérir
Assistance Publique Hôpitaux de Paris
FRM - Fondation Recherche Médicale
ERA-Net for Research Programmes on Rare Diseases
Agence nationale de la recherche
Région Ile-de-France
DIM Thérapie Génique
Fondation Jérôme Lejeune


The team also takes advantage from private partnerships

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