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Terapia genética para hemoglobinopatias
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As hemoglobinopatias constituem um grupo de doenças genéticas hereditárias, caracterizadas pela síntese deficiente ou alterações estruturais nas cadeias polipeptídicas da hemoglobina, que resultam numa função anormal desta proteína, essencial para o transporte de oxigénio para os tecidos. Entre as formas mais prevalentes, destacam-se a anemia falciforme e a β-talassemia major, que afetam milhares de pessoas em todo o mundo, particularmente em regiões com histórico de malária endémica. Estas patologias representam um desafio relevante em termos de saúde pública, não apenas pela sua prevalência, mas também pelo impacto significativo que têm na qualidade de vida dos doentes. As terapêuticas convencionais, como a hidroxiureia e as transfusões sanguíneas, são essenciais para o controlo das manifestações clínicas, mas não constituem um tratamento curativo, uma vez que não atuam na causa subjacente da doença, a mutação genética, e estão associadas a riscos a longo prazo. Neste contexto, a terapia genética surge como uma abordagem promissora e inovadora, com o objetivo de atuar diretamente na etiologia genética destas doenças. As principais estratégias incluem a adição de uma cópia funcional do gene da β-globina e a edição genética, com destaque para ferramentas como o sistema CRISPR/Cas, a base editing ou a prime editing. Estas abordagens têm demonstrado resultados promissores, que se traduzem no aumento da produção de hemoglobina funcional e na redução, ou até mesmo eliminação, das manifestações clínicas da doença. Apesar das limitações e desafios ainda existentes, os resultados científicos obtidos já permitiram a aprovação de terapias eficazes e seguras, como o Zynteglo®, Lyfgenia® e Casgevy®, que representam um ponto de viragem no tratamento das hemoglobinopatias. Atualmente, decorrem vários ensaios centrados na avaliação da segurança a longo prazo das terapias já aprovadas, bem como na investigação da eficácia e segurança de novas estratégias terapêuticas, incluindo a terapia genética in vivo, que se antevê como uma alternativa menos invasiva e mais acessível. Desta forma, a terapia genética representa uma nova era na medicina, com potencial para modificar profundamente o curso destas doenças e proporcionar uma melhoria significativa na qualidade de vida dos doentes.
Hemoglobinopathies constitute a group of hereditary genetic diseases, characterized by deficient synthesis or structural alterations in the polypeptide chains of hemoglobin, resulting in abnormal function of this protein, which is essential for the transport of oxygen to the tissues. Among the most prevalent forms are sickle cell anemia and β-thalassemia major, which affect thousands of people worldwide, particularly in regions with a history of endemic malaria. These pathologies represent a significant public health challenge, not only due to their prevalence but also because of the considerable impact they have on patients' quality of life. Conventional therapies, such as hydroxyurea and blood transfusions, are essential for controlling clinical manifestations, but they do not constitute a curative treatment, as they do not act on the underlying cause of the disease, the genetic mutation, and are associated with long-term risks. In this context, gene therapy emerges as a promising and innovative approach, aiming to act directly on the genetic etiology of these diseases. The main strategies include the addition of a functional copy of the β-globin gene and genetic editing, with emphasis on tools such as the CRISPR/Cas system, base editing, or prime editing. These approaches have shown promising results, leading to increased production of functional hemoglobin and a reduction or even elimination of the clinical manifestations of the disease. Despite the existing limitations and challenges, the scientific results obtained have already led to the approval of effective and safe therapies, such as Zynteglo®, Lyfgenia®, and Casgevy®, which represent a turning point in the treatment of hemoglobinopathies. Currently, several trials are underway focusing on the long-term safety assessment of already approved therapies, as well as on the investigation of the efficacy and safety of new therapeutic strategies, including in vivo gene therapy, which is anticipated to be a less invasive and more accessible alternative. In this way, gene therapy represents a new era in medicine, with the potential to profoundly modify the course of these diseases and provide a significant improvement in patient´s quality of life.
Hemoglobinopathies constitute a group of hereditary genetic diseases, characterized by deficient synthesis or structural alterations in the polypeptide chains of hemoglobin, resulting in abnormal function of this protein, which is essential for the transport of oxygen to the tissues. Among the most prevalent forms are sickle cell anemia and β-thalassemia major, which affect thousands of people worldwide, particularly in regions with a history of endemic malaria. These pathologies represent a significant public health challenge, not only due to their prevalence but also because of the considerable impact they have on patients' quality of life. Conventional therapies, such as hydroxyurea and blood transfusions, are essential for controlling clinical manifestations, but they do not constitute a curative treatment, as they do not act on the underlying cause of the disease, the genetic mutation, and are associated with long-term risks. In this context, gene therapy emerges as a promising and innovative approach, aiming to act directly on the genetic etiology of these diseases. The main strategies include the addition of a functional copy of the β-globin gene and genetic editing, with emphasis on tools such as the CRISPR/Cas system, base editing, or prime editing. These approaches have shown promising results, leading to increased production of functional hemoglobin and a reduction or even elimination of the clinical manifestations of the disease. Despite the existing limitations and challenges, the scientific results obtained have already led to the approval of effective and safe therapies, such as Zynteglo®, Lyfgenia®, and Casgevy®, which represent a turning point in the treatment of hemoglobinopathies. Currently, several trials are underway focusing on the long-term safety assessment of already approved therapies, as well as on the investigation of the efficacy and safety of new therapeutic strategies, including in vivo gene therapy, which is anticipated to be a less invasive and more accessible alternative. In this way, gene therapy represents a new era in medicine, with the potential to profoundly modify the course of these diseases and provide a significant improvement in patient´s quality of life.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2025, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
204205441 Hemoglobina Mutação Anemia falciforme Talassemia Terapia genética Mestrado integrado - 2025