Project: IL-18 and MRP neutralization for the treatment of anti-IL-1-refractory autoinflammatory diseases
| Acronym | Cure-AID |
| Project Topic | 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-IL1-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. |
| Network | E-Rare-3 |
| Call | 9th JOINT CALL FOR EUROPEAN RESEARCH PROJECTS ON RARE DISEASES (JTC 2017) |
Project partner
| Number | Name | Role | Country |
|---|---|---|---|
| 1 | Ghent University/VIB Center for Inflammation Research | Coordinator | Belgium |
| 2 | Westfälische Wilhelmsuniversität Münster | Partner | Germany |
| 3 | University Hospitals Geneva | Partner | Switzerland |
| 4 | University of Calgary | Partner | Canada |