公开(公告)号：US20230233553A1

公开(公告)日：2023-07-27

申请号：US18003783

申请日：2021-06-28

申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  FONDATION IMAGINE ,  Université Paris Cité ,  Assistance Publique-Hôpitaux de Paris (APHP) ,  University of Connecticut

发明人： Laurence LEGEAI-MALLET ,  Laurinda JAFFE ,  Leia SHUHAIBAR

IPC分类号： A61K31/496 ,  A61K38/22 ,  A61P19/08

CPC分类号： A61K31/496 ,  A61K38/2242 ,  A61P19/08

摘要： Activating mutations in fibroblast growth factor receptor 3 (FGFR3) and inactivating mutations in the natriuretic peptide receptor 2 (NPR2) guanylyl cyclase both result in decreased production of cyclic GMP (cGMP) and severe short stature, causing achondroplasia and acromesomelic dysplasia type Maroteaux, respectively. In attempt to find a new therapeutic approach for FGFR3-related skeletal disease, the inventors showed that a combination of a NPR2 agonist (e.g. BMN-111) and a phosphatase inhibitor (e.g. LB-100) significantly increases the length of the Fgfr3Y367C/+ femurs compared to Fgfr3+/+ femurs and improves the whole growth plate cartilage. The present invention thus relates to the use of a NPR2 agonist (e.g. BMN-111) and a phosphatase inhibitor (e.g. LB-100) for the treatment of FGFR3-related skeletal disease (e.g. achondroplasia).