Project: Cerebral Cavernous Malformations. From pathobiology to therapeutic strategies.

Cerebral Cavernous Malformations are among the most common vascular malformations of the brain, particularly in young people. CCMs can give rise to epileptic seizures and brain hemorhages and, although many of them are sporadic with no apparent cause, there is a significant subset that is caused by genetic mutations. Patients who suffer this familial form of the disease are riddled with multiple lesions. The severity of this disease is related to the lack of success of neurosurgery for lesions located in the deep part of the brain and also the spinal cord. Such lesions may lead to death or severe morbidity and novel pharmacological approaches are desperately needed for those severe forms of the disease which do not benefit from neurosurgery. The genes whose mutation is responsible for familial CCM development have been identified in recent years, and this has sparked interest in the study of their biology and the pathogenesis of CCMs. We know now that CCMs are important in the behaviour of the cells lining the brain vessels, or endothelial cells, and this has even led to the suggestion of possible pharmacological treatments of CCMs. However, there are still many unknowns about the function of the CCM genes and consequently about the biology of CCMs. Our teams have contributed to the understanding of CCM biology, and propose now to decipher the function of CCM proteins and the biology of CCMs, using an integrated approach, studying all three CCM genes at a time, and combining in vitro approaches and advanced animal models. This way, we intend to assess possible therapeutic strategies in mice that could be implemented in human patients afterwards. Four different European groups will be part of this consortium and collaborate tightly, each putting forward its own expertise.

Acronym	CCM
Duration	01/02/2012 - 31/07/2015
Network	NEURON
Call	NEURON-2011 Cerebrovascular Diseases

Project partner

Number	Name	Role	Country
1	German Cancer Research Center Heidelberg	Coordinator	Germany
2	INSERM	Partner	France
3	INSERM	Partner	France
4	University of Santiago de Compostela	Partner	Spain