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Advisor(s)
Abstract(s)
A insuficiência cardíaca é uma doença altamente complexa com um grande impacto na
qualidade de vida dos doentes, continuando a ser a principal causa de morbilidade e
mortalidade a nível mundial. Em Portugal estima-se que existam mais de 400000
indivíduos afetados. Acarreta também uma elevada pressão económica e sobre o sistema de
saúde.
Apesar de todos os avanços conseguidos na terapêutica convencional da insuficiência
cardíaca com consequente redução da mortalidade, as terapêuticas farmacológicas atuais
ou intervenções cirúrgicas não apresentam impacto na taxa de sobrevivência a cinco anos e
podem apresentar efeitos adversos indesejados, não se mostrando, portanto, eficazes.
Atualmente, os mecanismos fisiopatológicos insuficiência cardíaca já são bem conhecidos,
tendo sido identificadas várias vias moleculares que contribuem para o desenvolvimento
desta condição. Assim, a terapêutica genética é uma abordagem inovadora com elevado
potencial para o tratamento da insuficiência cardíaca. O objetivo da terapêutica genética
para a insuficiência cardíaca é inibir a apoptose celular, reduzir a remodelação cardíaca
adversa e aumentar a contratilidade cardíaca através da transfeção de cardiomiócitos
altamente eficiente.
Nas últimas décadas tem ocorrido um grande volume de investigação na área, o que
permitiu que os primeiros ensaios clínicos em humanos decorressem na última década.
Apesar do otimismo inicial, nenhum ensaio conseguiu cumprir os objetivos finais
delineados. Contudo, a área continua em evolução com novas descobertas contínuas.
Esta monografia irá explorar o estado atual da terapêutica genética para insuficiência
cardíaca, focando nos avanços mais recentes, desafios e possíveis direções futuras,
incluindo tecnologias emergentes, novos alvos e estratégias para melhorar a eficiência na
entrega de genes e a expressão de transgenes a longo prazo.
Heart failure is a highly complex disease with a significant impact on patients' quality of life, remaining the leading cause of morbidity and mortality worldwide. In Portugal, it is estimated that there are over 400,000 affected individuals. It also imposes a high economic burden and strains the healthcare system. Despite the advancements achieved in conventional therapy for heart failure, resulting in reduced mortality, current pharmacological therapies or surgical interventions have not shown an impact on five-year survival rates and may have undesired adverse effects, thus lacking efficacy. Currently, the pathophysiological mechanisms of heart failure are well-known, and several molecular pathways contributing to the development of this condition have been identified. Therefore, gene therapy is an innovative approach with great potential for the treatment of heart failure. The goal of gene therapy for heart failure is to inhibit cellular apoptosis, reduce adverse cardiac remodeling, and increase cardiac contractility through highly efficient transfection of cardiomyocytes. In recent decades, a significant volume of research has been conducted in this area, leading to the initiation of the first clinical trials in humans in the last decade. Despite the initial optimism, none of these trials have successfully achieved the intended endpoints. However, the field continues to evolve with ongoing new discoveries. This monograph will explore the current state of gene therapy for heart failure, focusing on the latest advancements, challenges, and potential future directions, including emerging technologies, new targets, and strategies to improve gene delivery efficiency and long-term transgene expression.
Heart failure is a highly complex disease with a significant impact on patients' quality of life, remaining the leading cause of morbidity and mortality worldwide. In Portugal, it is estimated that there are over 400,000 affected individuals. It also imposes a high economic burden and strains the healthcare system. Despite the advancements achieved in conventional therapy for heart failure, resulting in reduced mortality, current pharmacological therapies or surgical interventions have not shown an impact on five-year survival rates and may have undesired adverse effects, thus lacking efficacy. Currently, the pathophysiological mechanisms of heart failure are well-known, and several molecular pathways contributing to the development of this condition have been identified. Therefore, gene therapy is an innovative approach with great potential for the treatment of heart failure. The goal of gene therapy for heart failure is to inhibit cellular apoptosis, reduce adverse cardiac remodeling, and increase cardiac contractility through highly efficient transfection of cardiomyocytes. In recent decades, a significant volume of research has been conducted in this area, leading to the initiation of the first clinical trials in humans in the last decade. Despite the initial optimism, none of these trials have successfully achieved the intended endpoints. However, the field continues to evolve with ongoing new discoveries. This monograph will explore the current state of gene therapy for heart failure, focusing on the latest advancements, challenges, and potential future directions, including emerging technologies, new targets, and strategies to improve gene delivery efficiency and long-term transgene expression.
Description
Keywords
Insuficiência Cardíaca Terapêutica Genética da Insuficiência Cardíaca Terapêutica Genética:insuficiência Cardíaca Crónica