Joint Transnational Call 2014 (JTC2014)


Cerebral cavernous malformations (CCMs) are vascular lesions mostly located in the central nervous system, leading to epileptic seizures and hemorrhagic stroke. The disease occurs as a sporadic and a familial form. The autosomal dominant form of CCM has a prevalence of 1/10.000 and is characterized by the presence of multiple CCM lesions causing recurrent cerebral hemorrhages. Deep seated lesions are not accessible to neurosurgery and novel pharmacological approaches are desperately needed for those severe forms of the disease. Our collaboration supports the hypothesis that unbiased pharmacological suppression screens in the nematode C. elegans (Canadian partners) and in the small vertebrate model organism zebrafish (German partners) will help to identify compounds with a beneficial effect for the treatment or prevention of CCMs. By identifying compounds that suppress ccm mutant phenotypes in both C. elegans and zebrafish, we will gain insight into those molecular pathways and cell biological processes that are relevant for the CCM disease. The French partner has generated inducible murine knock out models that mimic human cerebral and retinal CCM lesions. The efficacy of the mostpromising compounds will be assessed in these mouse models. Our collaboration brings together the power of genetics of the C. elegans and zebrafish models with the murine disease models that are not suitable for unbiased high throughput compound screening. The added benefit of our transnational consortium is required for the identification of compounds with a beneficial effect in the CCM disease.

  • Seyfried, Salim (Coordinator)
    Hannover Medical School [GERMANY]
  • Von Kries, Jens Peter
    Leiniz-Institute for Molecular Pharmacology & Berlin Institute of Health [GERMANY]
  • Derry, Brent
    The Hospital for Sick Children & University of Toronto [CANADA]
  • J. Roy, Peter 
    University of Toronto [CANADA] 
  • Tournier-Lasserve, Elisabeth
    University Paris 7 Diderot [FRANCE]