Prophylactic and therapeutic agents for fgfr3 diseases and screening method for the same

Abstract

The present invention provides a therapeutic and/or prophylactic medicament for FGFR3 diseases, the medicament comprising a HMG-CoA reductase inhibitor as an active ingredient; a method for treating and/or preventing FGFR3 diseases, the method comprising administering a HMG-CoA reductase inhibitor; use of a HMG-CoA reductase inhibitor in the production of a therapeutic and/or prophylactic medicament for FGFR3 diseases; and a method for screening for a therapeutic and/or prophylactic drug for FGFR3 diseases.

1 - 15 . (canceled) 
     
     
         16 . A method for screening for a therapeutic and/or prophylactic drug for a FGFR3 disease, the method comprising the steps of:
 (a) differentiating induced pluripotent stem (iPS) cells having a FGFR3 mutation into chondrocytes under conditions where the cells are in contact with a test substance and under conditions where the cells are not in contact with the test substance,   (b) measuring one or more indicators selected from the group consisting of the amount of cartilaginous extracellular matrix, the expression level of a chondrocyte marker gene, and the expression level of a fibroblast marker gene in cultures resulting from step (a), and   (c) identifying the test substance as a therapeutic or prophylactic drug for a FGFR3 disease when the chondrocytes differentiated in contact with the test substance show an increased amount of the cartilaginous extracellular matrix, an increased expression level of the chondrocyte marker gene, or a decreased expression level of the fibroblast marker gene, as compared with the chondrocytes differentiated not in contact with the test substance.   
     
     
         17 . The method of  claim 16 , wherein step (a) for differentiation into chondrocytes comprises the steps of:
 (i) inducing mesodermal cells from pluripotent stem cells in adherent culture,   (ii) culturing the cells obtained by step (i) in adherent culture in a medium containing bFGF, ascorbic acid, BMP2, TGFβ, GDF5 and a test substance, and   (iii) culturing the cells obtained by step (ii) in suspension culture in a medium containing ascorbic acid, BMP2, TGFβ, GDF5 and the test substance.   
     
     
         18 . The method of  claim 16 , wherein the chondrocyte marker gene is one or more genes selected from the group consisting of SOX9, AGGRECAN and COL2. 
     
     
         19 . The method of  claim 16 , wherein the fibroblast marker gene is COL1A1 and/or COL1A2. 
     
     
         20 . The method of  claim 16 , wherein the FGFR3 mutation is Arg248Cys or Gly380Arg mutation in FGFR3. 
     
     
         21 . The method of  claim 16 , wherein the FGFR3 disease is thanatophoric dysplasia (TD) and/or achondroplasia (ACH).