Pharmacological intervention of the FGF-PTH axis as a potential therapeutic for craniofacial ciliopathies.

ABSTRACT: Ciliopathies represent a disease class characterized by a broad range of phenotypes including polycystic kidneys and skeletal anomalies. Ciliopathic skeletal phenotypes are among the most common and most difficult to treat due to a poor understanding of the pathological mechanisms leading to disease. Using an avian model (talpid2) for a human ciliopathy with both kidney and skeletal anomalies (orofaciodigital syndrome 14), we identified disruptions in the FGF23-PTH axis that resulted in reduced calcium uptake in the developing mandible and subsequent micrognathia. Although pharmacological intervention with the U.S. Food and Drug Administration (FDA)-approved pan-FGFR inhibitor AZD4547 alone rescued expression of the FGF target SPRY2, it did not significantly rescue micrognathia. In contras

SUBMITTER: Bonatto Paese CL 

PROVIDER: S-EPMC9403750 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature