Research projects

Hereditary Haemorrhagic Telangiectasia (HHT or Osler-Weber-Rendu Syndrome) is a hereditary dominant vascular disease that affects 1:2,000 or 3,000 patients in Spain, according to estimates from our own research group. It is characterised by frequent and recurring nosebleeds (epistaxis), red mucocutaneous patches (telangiectasia) and internal arteriovenous malformations that can affect the lungs, liver, brain and digestive tract. Endoglin and ALK-1 are the loci whose heterozygotic mutations cause 90% of these cases. Both genes code for receptors of the TGF-ß signalling complex and are expressed in the cells that line blood vessel walls (endothelial cells). Endoglin mutations cause HHT1, while ACVLR1/ALK-1 mutations cause HHT2. In both types, the phenotypical manifestations are similar due to the fact that the cell has an ALK1 and/or Endoglin deficiency. In Spain, work on this syndrome began in January 2003, within our research group, whereby an HHT unit was set up, making the Sierrallana Hospital (Torrelavega) a point of reference for the disease, an HHT Patients' Association set up in March 2005, and our Biological Research Centre (CSIC - Higher Scientific Research Centre) group, in charge of molecular diagnosis and study of the molecular mechanisms responsible for the pathogenicity of this disease. The patients are classified and diagnosed according to the clinical criteria of the reference hospital. This hospital sends blood samples to our group for molecular diagnosis and to establish primary cultures. Through this project, in addition to continuing with new HHT molecular diagnosis methods, we propose to apply pharmacological therapies in cultured cells derived from patients. Additionally, we have obtained primary cultures of endothelial peripheral blood cells from patients in our laboratory, being the only group in the world to have obtained said HHT cells. These cultures will serve as an in vitro model to develop drugs that will increase the expression of Endoglin and ALK1 in cases of deficiency. On the other hand, we will apply cellulogenic therapies to laboratory animals. For this purpose, injections of non-HHT infected cells will be administered in the tails of mice: immune system cells (macrophages) capable of differentiating themselves into vascular cells or endothelial cells derived from peripheral blood. Animal disease models will be comprised of mice with Endoglin and ALK-1 mutations. The analysis of the evolution and degree of recovery of the vascular damage in the mice, by inclusion of healthy cells, seeks to test HHT cellulogenic therapies.