Community Research and Development Information Service - CORDIS

Final Report Summary - CVM THERAPY (Angiogenesis Research to Improve Therapies for Vascular Malformations)

Congenital Vascular Malformations (CVM) are a group of diseases characterized by an inborn, localized defects of vascular morphogenesis. Occurring mainly on the face or other highly visible part of the body, the presence of CVM can cause emotional and social problems. Moreover, some malformations are painful or even life-endangering. Current treatments do not achieve optimal or long-lasting results. Thus, there is a pressing need for therapies that are more effective for these disfiguring lesions. Currently, the cellular components of the CVM have not been isolated and analyzed, and there is no animal model for most CVM.

The goal of my research was to isolate and characterize the endothelial cells, the major cellular component of the vascular malformations in order to develop targeted therapy for these lesions.
During the project period we were able to collect tissues from over 30 patients with vascular malformations. These malformations included lymphatic malformations, lymphangiomatosis, arterial-venous malformations (AVM), angiokeratoma and venous malformations (VM). By isolating pure population of pathogenic EC and employing high- throughput genome sequencing technologies we were able to identify a molecular cause for one of the most aggressive vascular anomalies (submitted). Our results show that mutation that probably occurred during embryonic development led to abnormal phenotype of the Lymphatic endothelial cells. This includes higher proliferation, increased survival, defective migration towards VEGF and decreased capacity to form proper vessels. Similar pathologies, including improper creation of lymphatic system are observed in a zebrafish model. Furthermore, our in vitro and in vivo results suggest that drugs blocking the mTOR and the MEK pathway can be used to treat several vascular malformations.

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Eve Keret, (Research Grants Coordinator)
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Record Number: 182595 / Last updated on: 2016-05-11
Information source: SESAM