Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Pharmacological intervention of the FGF-PTH axis as a potential therapeutic for ciliopathies 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 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. While pharmacological intervention with the FDA-approved pan-FGFR inhibitor AZD4547 alone rescued expression of the FGF target Sprouty2, it did not significantly rescue micrognathia. In contrast, treatment with a cocktail of AZD4547 and Teriparatide acetate, a PTH agonist and FDA-approved treatment for osteoporosis, resulted in a molecular, cellular, and phenotypic rescue of ciliopathic micrognathia in talpid2 mutants. Together, these data provide novel insight into pathological molecular mechanisms associated with ciliopathic skeletal phenotypes and a potential therapeutic strategy for a pleiotropic disease class with limited to no treatment options.

Summary StatementTreatment options for ciliopathic phenotypes are very limited. Using an avian model, we report a novel molecular mechanism and potential therapeutic treatment for ciliopathic micrognathia.
25
The categories of this paper are: bioengineering
24
The categories of this paper are: cancer
17
The categories of this paper are: molecular
13
The categories of this paper are: animal
23
The categories of this paper are: immunology
0
The categories of this paper are: genetics
27
The categories of this paper are: pathology
1
The categories of this paper are: bioinformatics
32
The categories of this paper are: zoology
12
The categories of this paper are: behavior
31
The categories of this paper are: paleontology
21
The categories of this paper are: toxicology
16
The categories of this paper are: microbiology
19
The categories of this paper are: epidemiology
11
The categories of this paper are: cognition
3
The categories of this paper are: evolutionary