Indication

Target/marker/pathway

Summary

Licensing status

Publication and contact information

Renal disease

Renal disease

Centrosomal protein 290 kDa (CEP290)

Mouse and cell culture studies suggest hedgehog pathway agonists could help treat Joubert syndrome, a genetic cerebellar disorder that causes renal failure and other symptoms. A mouse model of Joubert syndrome was generated from embryonic stem cells carrying a disruption in Cep290, the most common mutation in Joubert syndrome. The mice showed downregulation of the hedgehog pathway and a ciliopathy phenotype similar to the human syndrome, including retinal degeneration, cerebellar abnormalities and progressive polycystic kidney disease. In ex vivo cultures of collecting duct cells from the model and renal epithelial cells from patients with Joubert syndrome, a hedgehog pathway agonist improved spheroid formation and increased numbers of cilia compared with no treatment. Ongoing work includes identifying less toxic agonists by screening small compound libraries in cell-based assays.

SciBX 7(28); doi:10.1038/scibx.2014.837
Published online July 24, 2014

Unpatented; licensing status not applicable

Hynes, A.M. et al. Proc. Natl. Acad. Sci. USA; published online June 19, 2014;
doi:10.1073/pnas.1322373111
Contact: John A. Sayer, Newcastle University, Newcastle upon Tyne, U.K.
e-mail:

john.sayer@ncl.ac.uk