A Soluble Fibroblast Growth Factor Receptor 3 (FGR3) Polypeptide For Use In The Prevention Or Treatment Of Skeletal Growth Retardation Disorders

Abstract

The present invention relates to the prevention or treatment of skeletal growth retardation disorders, in particular skeletal diseases, developed by patients that display abnormal increased activation of the fibroblast growth factor receptor 3 (FGFR3), in particular by expression of a constitutively activated mutant of FGFR3. More particularly, the present invention relates to a soluble FGFR3 for use in the prevention or treatment of achondroplasia.

1 . An isolated soluble Fibroblast Growth Factor Receptor 3 (sFGFR3) polypeptide or a functional equivalent thereof for use in the prevention or treatment of a skeletal growth retardation disorder. 
     
     
         2 . The polypeptide for use according to  claim 1 , wherein the skeletal growth retardation disorder is an idiopathic growth retardation disorder. 
     
     
         3 . The polypeptide for use according to  claim 1 , wherein the skeletal growth retardation disorders is a FGFR3-related skeletal disease. 
     
     
         4 . The polypeptide for use according to  claim 3 , wherein the FGFR3-related skeletal disease is selected from the group consisting of thanatophoric dysplasia type I, thanatophoric dysplasia type II, severe achondroplasia with developmental delay and acanthosis nigricans, hypochondroplasia, achondroplasia and FGFR3-related craniosynostosis such as Muenke syndrome and Crouzon syndrome with acanthosis nigricans. 
     
     
         5 . The polypeptide for use according to  claim 4 , wherein the FGFR3-related skeletal disease is achondroplasia. 
     
     
         6 . The polypeptide for use according to  claim 3 , wherein the FGFR3-related skeletal disease is caused by expression in the subject of a constitutively active FGFR3 receptor mutant. 
     
     
         7 . The polypeptide for use according to  claim 6 , wherein the FGFR3-related skeletal disease is achondroplasia and the constitutively active FGFR3 receptor mutant is a mutant wherein the glycine residue at position 380 is substituted with arginine (named G380R). 
     
     
         8 . The polypeptide for use according to  claim 1 , wherein the polypeptide is encoded by the polypeptide sequence defined by SEQ ID NO: 1. 
     
     
         9 . The polypeptide for use according to  claim 8 , wherein the polypeptide sequence is encoded by a polynucleotide sequence defined by SEQ ID NO: 2. 
     
     
         10 . A pharmaceutical composition comprising an isolated sFGFR3 polypeptide or a functional equivalent thereof and a pharmaceutically acceptable carrier. 
     
     
         11 . (canceled) 
     
     
         12 . A method for preventing or treating a skeletal growth retardation disorder comprising the step of administering a therapeutically effective amount of a sFGFR3 polypeptide or a pharmaceutical composition comprising such polypeptide to a subject in need thereof.