Epidemiology, Pharmacology, New Therapies & Clinical Research
Molecular Diagnosis & Therapy
Researchers Rafael Parra, Irene Corrales, Lluis Martorell, Carme Altisent | Researcher in training Nina Borras | Technician Lorena Ramírez, Natàlia Comes
Among the most important achievements of our group in 2015, we can highlight the in-deep analysis of the molecular study of all patients enrolled in the National Registry for Clinical and Molecular Profile of von Willebrand Disease in Spain (PCM-EVW-ES), a multicenter project that involves the largest Spanish hospitals and that recruited more than 550 patients suffering from different types of VWD. The application of the high-throughput NGS technology to perform the molecular diagnosis of a large cohort of patients is providing invaluable results for a powerful investigation in the pathophysiological mechanisms of VWD in correlation with molecular defects, shedding light on the complex genotype-phenotype relationship.
Furthermore, we have underway the development of the study awarded by the 2013 European ASPIRE Hemophilia Awards (Pfizer), entitled “Development of a high-throughput platform for Hemophilia A drug screening and gene correction using induced pluripotent stem cells (iPSCs) from patients”. The project is based on the technology developed and in the knowledge acquired during the progress of a European transnational coordinated project (HEMO-iPS) funded by E-Rare-2 (ERA-Net for Research on Rare Diseases). The overall objective is focused on the development of optimized molecular tools to perform functional studies related to the production, processing, secretion, and half-life of FVIII in disease-relevant cells from hemophilia patients.
Finally, the advent of NGS has opened the possibility to design custom protocols for molecular analysis of several genes in parallel. This approach is particularly valuable in the diagnosis of diseases with similar phenotype although caused by a heterogeneous molecular basis. Taking advantage of this novel opportunity, we designed custom panel to simultaneously analyze the 23 essential genes involved in inherited bleeding disorders. This versatile approach simplifies routine procedure and is especially helpful when clinical diagnosis was unclear or controversial due to a borderline phenotype with various candidate genes. The ultimate goal will be the integration of this data to refine the knowledge of genotype-phenotype correlation and improve the forecasting of hemorrhagic risk.