Infigratinib for treatment of fgfr3-related skeletal diseases during pregnancy

Abstract

FGFR3 gain-of-function mutations are responsible for a family of chondrodysplasias namely, achondroplasia (ACH) the most common form of dwarfism, a lethal form of dwarfism thanatophoric dysplasia (TD) as well as and hypochondroplasia. Recent data demonstrate that Infigratinib (NVP-BGJ398) corrects pathological hallmarks of ACH and support it as a 10 potential therapeutic approach for FGFR3-related skeletal diseases. Now the inventors has investigated the feasibility to treat the defective growth of the skeleton during the pregnancy with the drug. They treated pregnant female Fgfr3Neo/Y367C mice with the drug (4 mg/kg) that was injected subcutaneously at day E14.5 continuing daily through day 1 (after birth). The data indicated that BGJ398 treatment during 5 days in pregnant mice successfully repressed skeletal 15 anomalies that occurred during embryonic stages. Accordingly, the present invention relates to methods for treatment of FGFR3-related skeletal diseases during pregnancy with Infigratinib.

1 . A method of treating a FGFR3-related skeletal disease in a fetus comprising administering to the pregnant subject an effective amount of Infigratinib. 
     
     
         2 . The method of  claim 1  wherein the FGFR3-related skeletal disease is a FGFR3-related chondrodysplasia. 
     
     
         3 . The method of  claim 2  wherein the FGFR3-related chondrodysplasia is selected from the group consisting of thanatophoric dysplasia type I, thanatophoric dysplasia type II, hypochondroplasia, achondroplasia, severe achondroplasia with developmental delay and acanthosis nigricans, and hypochondroplasia. 
     
     
         4 . The method of  claim 1  wherein the FGFR3-related skeletal disease is a FGFR3-related craniosynostosis. 
     
     
         5 . The method of  claim 4  wherein the FGFR3-related craniosynostosis is Muenke syndrome. 
     
     
         6 . The method of  claim 1  wherein Infigratinib is orally or subcutaneously administered to the pregnant subject.