Project: Targeting the unknowns in causes and phenotypes of the Cornelia de Lange Syndrome

The primordial CXCL12/CXCR4 chemokine/receptor pair is essential for embryogenesis and is involved in the control of numerous physiological and pathological processes. In 2003, dysfunctions (i.e. enhanced responses to CXCL12) were associated with the syndrome of Warts, Hypogammaglobulinemia, Infections and Myelokathexis (WHIM), described in the early 1960’s and which is an unusual form of neutropenia with hyperplasia of mature neutrophils in the bone marrow. Mostly linked to inherited heterozygous autosomal dominant CXCR4 mutations, the WHIM is however genetically and clinically heterogeneous thus impairing a straightforward diagnosis. Current treatments are mostly prophylactic and do not specifically target the CXCL12/CXCR4 pair although there is strong support now for the responsibility of dysfunctions of this axis in WHIM pathogenesis. In principle, inhibitors of the CXCL12/CXCR4 axis should be beneficial. The number of inhibitors remains limited and, although one has made the proof of concept of its acute use in the clinic for mobilization of bone marrow stem cells, we do not know what the consequences of chronic inhibition of the CXCL12-dependent axis would be. Thus, our aims are 1) to diffuse knowledge about WHIM and improve patients’ access to diagnosis and treatment; 2) to develop a transnational synergy to establish patient databases, collect biological material and define key markers of the disease; 3) to make the proof of concept of the impact of CXCL12/X4-blockade and 4) to elaborate, characterize and test novel antagonists of this axis into cell and mouse models

Duration 01/01/2013 - 31/12/2015
Project Topic 4th JOINT CALL FOR EUROPEAN RESEARCH PROJECTS ON RARE DISEASES (JTC 2012) (Driven by young investigators)
Network E-Rare-2
Call 4th Joint Call for European Research Projects on Rare Diseases driven by Young Investigators

Project partner

Number Name Role Country
1 University of Lübeck Coordinator Germany
2 Erasmus MC Partner Netherlands
3 Faculté de Médecine de Rennes Partner France