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A breakthrough for treating genetic skeletal dysplasia |Institute of Cellular and Organismic Biology, Academia Sinica


A breakthrough for treating genetic skeletal dysplasia

Have you ever wished you were taller? Dr. Yi-Ching Lee led a team developed a screening system to identify bioactive compounds from plant extracts that may help achondroplasia patients grow taller.

Overactivation mutations in FGFR3 lead to a group of short-limbed dwarfism and certain types of cancer. Achondroplasia is the most common form of human dwarfism caused by FGFR3 overactivation mutations. Targeting FGFR3 activity offers a promising therapeutic approach for managing of these conditions. The team developed a cell-based screening system to specifically monitor FGFR3 activation and used it to find natural FGFR3 modulators from plant extracts. They discovered a plant extract that reduced FGFR3 activity and identified 2 bioactive compounds, including Pa, from the extract. Further analysis revealed that Pa enhanced FGFR3 degradation and reduced excessive FGFR3 signaling in FGFR3-overactivated cancer cells and chondrocytes. Pa not only inhibits the cell growth of FGFR3-overactivated cancer cells but also helps to improve the defective growth of long bones in bone cultures of humanized achondroplasia mice. This research presents an approach for the discovery and verification of plant extracts or drug candidates that target at FGFR3 activation. Compounds identified by this approach have the potential to be developed into therapeutics for FGFR3-associated cancers and bone disorders.

This work was supported by Academia Sinica and National Science and Technology Council (NSTC) of Taiwan. The research team includes graduate student Yun-Wen Lin, research assistant Wei-Ting Chen, Dr. Cheng-Fu Kao and Dr. Yi-Ching Lee from the Institute of Cellular and Organismic Biology, and Dr. Hsiao-Jung Kao, Dr. Jer-Yuarn Wu, and Dr. Yuan-Tsong Chen from the Institute of Biomedical Sciences at Academia Sinica. Patents are pending in several countries for the screening platform, the humanized achondroplasia mouse model, the plant extracts, the bioactive compounds and their derivatives described in this research.