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Infigratinib for treatment of fgfr3-related skeletal diseases during pregnancy

a technology of fgfr3 and infigratinib, which is applied in the direction of skeletal disorders, drug compositions, medical preparations, etc., can solve the problems of defective development and growth of the mandibl

Pending Publication Date: 2022-02-10
UNIVERSITÉ PARIS CITÉ +3
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Benefits of technology

The patent is about methods for treating bone diseases related to FGFR3 during pregnancy. The technical effects of the patent are assisting in the prevention and treatment of bone problems in pregnant women who have certain genetic markers.

Problems solved by technology

Meckel's and condylar cartilages anomalies in achondroplasia result in defective development and growth of the mandible.

Method used

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  • Infigratinib for treatment of fgfr3-related skeletal diseases during pregnancy
  • Infigratinib for treatment of fgfr3-related skeletal diseases during pregnancy
  • Infigratinib for treatment of fgfr3-related skeletal diseases during pregnancy

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Introduction

[0020]FGFR3-related chondrodysplasias encompass the most frequent chondrodysplasias (achondroplasia and hypochondroplasia) and Craniosynostoses (Muenke syndrome). All these osteochondrodysplasias are due to Fgfr3 germinal mutations, these Fgfr3 gain-of-function mutations impair the chondrogenesis and osteogenesis during the formation of the skeleton.

[0021]Objective of the Study:

[0022]To demonstrate that it is feasible to treat with the BGJ398 the defective growth of the skeleton during the pregnancy.

[0023]Materials and Methods:

[0024]The efficacy of BGJ398 treatment on skeletal development was demonstrated previously on Fgfr3Y367C / + pups exhibiting dwarfism (Komla-Ebri et al 2016, Biosse-Duplan et al 2016).

[0025]We treated pregnant female Fgfr3Neo / Y367C mice that were mated with CreCMV / + male mice (Pannier, S., Couloigner, V., Messaddeq, N., Elmaleh-Bergès, M, Munnich, A., Romand, R., & Legeai-Mallet, L. (2009). Activating Fgfr3 Y367C mutation causes hearing loss and inne...

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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.

Description

FIELD OF THE INVENTION[0001]The present invention relates to methods for treatment of FGFR3-related skeletal diseases during pregnancy.BACKGROUND OF THE INVENTION[0002]Fibroblast growth factor receptors (FGFRs) are a family of five receptor tyrosine kinases (RTKs) and are important regulators of skeleton development during endonchondral and membranous ossification throughout embryonic and postnatal development. FGFR3 is expressed in both bone and cartilage and FGFR3 signaling regulates a variety of biological events during skeletal development. 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 (HCH). Pathogenic dominant FGFR3 mutations also cause craniosynostosis. Muenke syndrome is the most common craniosynostosis syndrome and Crouzon syndrome associated with acanthosis nigricans (CAN) is a rare syndr...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/506A61P19/00
CPCA61K31/506A61P19/00
Inventor LEGEAI-MALLET, LAURENCE
Owner UNIVERSITÉ PARIS CITÉ
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