Ponente: Carlos Carrascoso. Division of Innovative Therapies in the Hematopoietic System, CIEMAT and Advanced Therapies Unit, IIS-FJD. Instituto de Investigaciones Biomédicas Alberto Sols (CSIC/UAM). Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER).
Resumen: X-linked dyskeratosis congenita (X-DC) is a low prevalent inherited bone marrow failure syndrome mainly caused by point mutations in DKC1 gene, which encodes for the dyskerin nucleolar protein. These mutations impair telomerase activity leading to premature telomere length attrition, for this reason DC is also classified as a telomere biology disorder. The hardly access to patients samples and its reduced content in hematopoietic stem cells (HSCs) lead us to generate DKC1-low CD34+ cells using specific anti-DKC1 short hairpin RNAs (shRNAs) to knock down the expression of dyskerin in HSCs derived from umbilical cord blood. This model will provide a base for the better understanding of the HSC defects characteristic of this disease. Furthermore, the major cause of premature death in X-DC patients is bone marrow failure (BMF) and the only curative treatment for BMF is allogeneic hematopoietic stem cell transplantation. However, risks derived from conditioning regimes, graft versus host disease and the difficulties to find compatible donors severely compromise this therapeutic approach. In this way, we propose two promising gene therapy approaches based on autologous transplantation of gene modified HSCs able to correct the BMF characteristic of X-DC patients.