Achondroplasia is the most common form of human dwarfism. The molecular basis of achondroplasia was elucidated in 1994 with the identification of the fibroblast growth factor receptor 3 (FGFR3) as the causative gene. Missense mutations causing achondroplasia result in activation of FGFR3 and its downstream signaling pathways, disturbing chondrogenesis, osteogenesis, and long bone elongation. A more accurate understanding of the clinical and molecular aspects of achondroplasia has allowed new therapeutic approaches to be developed. These are based on: clear understanding of the natural history of the disease; proof-of-concept preclinical studies in mouse models; and the current state of knowledge regarding FGFR3 and related growth plate homeostatic pathways. This review provides a brief overview of the preclinical mouse models of achondroplasia that have led to new, non-surgical therapeutic strategies being assessed and applied to children with achondroplasia through pioneering clinical trials.
Keywords: Achondroplasia; Clinical trials; FGFR3; Mouse models; Preclinical studies; Therapeutic approaches.
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