Pluripotent Stem Cells in Disease Modeling and Drug Discovery for Myotonic Dystrophy Type 1.
Noémie Bérenger-CurriasCécile MartinatSandrine BaghdoyanPublished in: Cells (2023)
Myotonic dystrophy type 1 (DM1) is a progressive multisystemic disease caused by the expansion of a CTG repeat tract within the 3' untranslated region (3' UTR) of the dystrophia myotonica protein kinase gene ( DMPK ). Although DM1 is considered to be the most frequent myopathy of genetic origin in adults, DM1 patients exhibit a vast diversity of symptoms, affecting many different organs. Up until now, different in vitro models from patients' derived cells have largely contributed to the current understanding of DM1. Most of those studies have focused on muscle physiopathology. However, regarding the multisystemic aspect of DM1, there is still a crucial need for relevant cellular models to cover the whole complexity of the disease and open up options for new therapeutic approaches. This review discusses how human pluripotent stem cell-based models significantly contributed to DM1 mechanism decoding, and how they provided new therapeutic strategies that led to actual phase III clinical trials.
Keyphrases
- end stage renal disease
- clinical trial
- stem cells
- chronic kidney disease
- ejection fraction
- newly diagnosed
- phase iii
- pluripotent stem cells
- drug discovery
- prognostic factors
- peritoneal dialysis
- open label
- endothelial cells
- early onset
- induced apoptosis
- skeletal muscle
- multiple sclerosis
- randomized controlled trial
- depressive symptoms
- copy number
- cell proliferation
- adipose tissue
- metabolic syndrome
- type diabetes
- dna methylation
- physical activity
- phase ii
- patient reported
- study protocol
- patient reported outcomes
- cell therapy