Funding transnational collaborative research through joint transnational calls is one of the major objectives of E-Rare. This is the most important and effective joint activity to enhance the cooperation between European scientists working on rare diseases and thus reducing the fragmentation of research in this field. E-Rare launches calls on a yearly basis. The topic and eligibility criteria are specified every year and therefore may vary from one call to the other.

Cysteamine for the treatment of cystic fibrosis: a translational research project

Project Coordinator

Ospedale San Raffaele


Guido Kroemer Inserm, U1038 Centre de Recherche des Cordeliers Villejuif, France
Eitan Kerem Hadassah-Hebrew University Medical Center Jerusalem, Israel

The proposed approach focuses on a bottom-up, cost-effective strategy of drug discovery in CF in which drugs already approved for other human diseases or natural compounds with well known safety profile, are combined to reverse the alterations of proteostasis resulting from the loss-of-function mutation of CFTR. We aim at setting up a translational proof-of-concept for a rationale-based combination of proteostasis modifiers in the therapy of CF patients, as well as at validating a prediction test of the responsiveness of each individual patient to candidate drugs for CF therapy. We will use a multifaceted pre-clinical approach implicating animal models of CF, as well as primary nasal epithelial cells from CF patients harbouring different CFTR mutants. We have demonstrated that cystamine restores mismanaged proteostasis and deficient autophagy resulting from defective CFTR function and that cystamine can rescue and stabilize F508del at the cell membrane, an effect that can persists for days after drug withdrawal. Herein, we will test how long the effects of cysteamine the reduced form of cystamine, a FDA-approved drug for therapy of cystinosis, might persist after washout and how these effects may be prolonged. We also aim at deciphering the mechanisms through which small molecules with known safety profile might extend the action of cysteamine. We will select small molecules capable to inhibit the Casein-kinase 2, a major culprit of CFTR fragmentation and poor stability. Altogether, this strategy should delineate novel therapeutic options for the treatment of CF.

E-Rare 2012 - Created by Toussaint Biger