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.

Belgium
Switzerland
Germany
Canada
Cure-AID
IL-18 and MRP neutralization for the treatment of anti-IL-1-refractory autoinflammatory diseases

Project Coordinator

Ghent University/VIB Center for Inflammation Research
Ghent
Belgium

Partners

Johannes Roth Westfälische Wilhelmsuniversität Münster Muenster, Germany
Cem Gabay University Hospitals Geneva Geneva, Switzerland
Paul Kubes University of Calgary Calgary, Canada

Autoinflammatory diseases (AID) are a group of devastating systemic inflammatory syndromes characterized by seemingly unprovoked episodes of severe inflammation without signs of classical autoimmunity. The general prevalence of AID is below 1:100,000 individuals. As the genes mutated in AID are increasingly being mapped, inflammasome signalling and the cytoskeletal network are emerging as key mechanisms responsible for AID. Excess interleukin (IL)-1β production has a primary pathogenic role in select AID (exemplified by CAPS), but IL-1 neutralization therapies are ineffective or only partially effective in the majority of AID patients. Thus, there is a high, unmet need for development of novel therapies to treat IL-1-refractory AID and devastating AID-associated complications such as macrophage activation syndrome (MAS). Our consortium has classified a subset of AID patients with selective and highly elevated IL-18 and MRP8/14 in circulation. These inflammatory mediators are hypothesized to support a vicious inflammatory cycle in anti-IL-1-refractory AID. The consortium has at its disposal a unique set of preclinical therapeutic agents, as well as cellular and in vivo models of non-classical AID, that will be exploited to address the therapeutic potential of IL-18 and MRP neutralization strategies in single and combination regimens. Finally, we will address how modulation of cytoskeleton dynamics and immune cell activation may affect IL-18 and MRP8/14 secretion as a therapeutic strategy in AID mouse models using cutting-edge in vivo imaging.

E-Rare 2012 - Created by Toussaint Biger