【演者】Véronique M.A. Lefebvre先生（Research Professor, Department of Surgery, Division of Orthopaedic Surgery, Translational Program in Pediatric Orthopaedics, Chi）【演題】Advancing Science to offer new therap

第53回システム発生・再生医学分野セミナー 本学対面形式にて開催しました

日時：令和7年9月12日（金）17:00-18:00 要旨：Skeletal disorders exist in hundreds of forms, rare or frequent, mild or severe. Altogether, they impact the quality of life of many human beings. Yet, our understanding of pathogenic mechanisms and abilities to offer safe and efficacious treatments remain limited for most disorders. This talk will focus on our recent efforts to fill gaps regarding achondroplasia, the most prevalent form of short stature. It is due to missense variants over-activating the fibroblast growth factor receptor-3, which negatively regulates skeletal growth. Beside skeletal disproportions, achondroplasia also causes severe neurological complications. As current surgical and pharmaceutical treatments only partially improve discrete disease features, we sought to explore other approaches. We found that a highly conserved Fgfr3 enhancer was sufficient to activate a reporter gene in the cartilage-specific domain of Fgfr3 expression and that its deletion in wild-type mice significantly reduced Fgfr3 expression. Importantly, its deletion in mice harboring a prevalent achondroplasia variant largely normalized long bone and vertebral body growth, reduced spinal canal and foramen magnum stenosis, and improved craniofacial defects. Mice were healthy throughout life. Taken together, these findings open a path to genetic therapies for achondroplasia and suggest that similar approaches could also be developed for many other diseases.