The project applies to the call HEALTH-2007-2.4.4. – Rare diseases whose expected impact is ” (i) to shed light on the course and/or mechanisms of rare diseases, or (ii) to test diagnostic, preventive and/or therapeutic approaches, to alleviate the negative impact of the disease on the quality of life of the patients and their families”.

In particular, this project addresses the topic HEALTH-2007-2.4.4-1: Natural course and pathophysiology of rare diseases.

Ciliary disorders are rare mendelian disorders. In particular, OFDI has been reported to have an incidence of 1:250000, BBS has a prevalence of 1:70000 and for NPHP the incidence is estimated at less than 1:100000.
The EUCILIA consortium is interested in the pathophysiology of these ciliopathies with specific emphasis on the development of renal cysts by developing and studying appropriate animal models (WP1), by developing in vitro models (WP2), and by studying signalling pathways to understand cilia assembly and to determine protein interaction networks to establish a hierarchy of temporal and spatial interactions of BBS, OFDI, and NPHP proteins in cilium structure and function (WP3, WP4). Furthermore, the project is exploring the possibility to utilize alternative vertebrate models to the mouse, namely Xenopus and zebrafish, to study novel signalling pathways that regulate cilia function (WP5). Finally, EUCILIA proposes to identify and evaluate potential therapeutic agents to prevent or reverse renal cyst formation that might influence the life of patients with severe kidney disease due to ciliary dysfunction (WP6).

The topic of the call also specifically states to focus on “diseases principally affecting the genitourinary tract”. All ciliary disorders have an important renal involvement that is the most life threatening symptom of the disease. The project focuses on three groups of rare and heritable ciliary disorders, namely BBS, OFDI and NPHP. Each of these disorders present with defining features but are all characterized by the presence of polycystic renal disease. Renal cysts, as those developed in BBS, OFD and NPHP, result in severe kidney failure. The proteins encoded by the genes responsible for these genetic disorders, as well as those implicated in heritable forms of cystic kidneys, are all located to the cilium/basal body/centrosome complex, suggesting that ciliary dysfunction might be the unifying pathogenic concept underlying cystic kidney disease.
Polycystic kidney diseases (PKD) are a leading cause of end-stage renal failure and a common indication for dialysis or renal transplantation. Only further comprehension into the role of ciliary proteins will help understand the pathomechanism of the disease and have an impact on the clinical management of patients.