Descripción del proyecto
Estimular la regeneración tisular podría ofrecer una «cura» para el ataque al corazón
El ataque al corazón, cuyo término científico es infarto de miocardio, se debe principalmente a una privación repentina de riego sanguíneo al músculo cardíaco. El tejido, privado de oxígeno y nutrientes, se necrosa y forma tejido cicatricial al cabo de varias semanas. El daño permanente puede debilitar al corazón y menoscabar su capacidad de bombear eficazmente la sangre. El proyecto CuRE, financiado con fondos europeos, está buscando un avance revolucionario en el tratamiento de esta afección prevalente, concretamente una terapia que estimule la regeneración de las células cardíacas activas. El equipo, que empezará con bibliotecas de factores que podrían tener este efecto, utilizará una combinación de ensayos «in vitro» e «in vivo» que lleven a la identificación de los más eficaces y al desarrollo de una terapia adecuada basada en ellos.
Objetivo
Biotechnological therapies for patients with myocardial infarction and heart failure are urgently needed, in light of the breadth of these diseases and a lack of curative treatments. CuRE is an ambitious project aimed at identifying novel factors (cytokines, growth factors, microRNAs) that promote cardiomyocyte proliferation and can thus be transformed into innovative therapeutics to stimulate cardiac regeneration. The Project leads from two concepts: first, that cardiac regeneration can be obtained by stimulating the endogenous capacity of cardiomyocytes to proliferate, second that effective biotherapeutics might be identified through systematic screenings both in vivo and ex vivo. In the mouse, CuRE will take advantage of two unique arrayed libraries cloned in adeno-associated virus (AAV) vectors, one corresponding to the secretome (1200 factors) and the other to the miRNAome (800 pri-miRNA genes). Both libraries will be functionally screened in mice to search for factors that enhance cardiac regeneration. This in vivo selection approach will be complemented by a series of high throughput screenings on primary cardiomyocytes ex vivo, aimed at systematically assessing the involvement of all components of the ubiquitin/proteasome pathway, the cytoskeleton and the sarcomere on cell proliferation. Cytokines and miRNAs can both be developed to become therapeutic molecules, in the form of recombinant proteins and synthetic nucleic acids, respectively. Therefore, a key aim of CuRE will be to establish procedures for their production and administration in vivo, and to assess their efficacy in both small and large animal models of myocardial damage. In addition to this translational goal, the project will entail the successful achievement of several intermediate objectives, each of which possesses intrinsic validity in terms of basic discovery and is thus expected to extend technology and knowledge in the cardiovascular field beyond state-of-the art.
Ámbito científico
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Programa(s)
Régimen de financiación
ERC-ADG - Advanced GrantInstitución de acogida
WC2R 2LS London
Reino Unido