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Avanços terapêuticos na doença de Alzheimer
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A Doença de Alzheimer é a patologia neurodegenerativa mais prevalente a nível global, sendo responsável por 60 a 80% dos casos de demência. A sua etiologia complexa e multifatorial, que envolve uma combinação de fatores genéticos, ambientais e condições relacionadas com o estilo de vida, torna o diagnóstico, o tratamento e a prevenção particularmente desafiantes. A evolução do conhecimento dos mecanismos fisiopatológicos subjacentes a esta doença tem impulsionado o desenvolvimento de novas estratégias terapêuticas, que vão além do alívio sintomático proporcionado pelo tratamento convencional, nomeadamente os inibidores da acetilcolinesterase e a memantina. As terapias emergentes procuram interferir nos processos biológicos centrais da patologia, como a deposição do péptido β-amilóide, a disfunção da proteína tau, a neuroinflamação, entre outros, visando modificar a progressão da doença. A aprovação de três anticorpos monoclonais anti-amilóide - aducanumab, lecanemab e donanemab - pelas entidades reguladoras como a Food and Drug Administration (FDA) e a European Medicines Agency (EMA) abre caminho para o desenvolvimento de outras terapias modificadoras da doença, enquanto reforça e encoraja os esforços de investigação na procura de estratégias mais eficazes e duradouras. Nesta monografia é discutida a fisiopatogenia da doença, as técnicas de diagnóstico atuais e os avanços terapêuticos mais recentes. São ainda abordados os ensaios clínicos mais promissores, as perspetivas futuras e os principais desafios associados ao desenvolvimento e implementação de novos fármacos para o tratamento da doença de alzheimer.
Alzheimer’s Disease is the most prevalent neurodegenerative disorder worldwide, accounting for 60 to 80% of dementia cases. Its complex and multifactorial etiology, involving a combination of genetic, environmental, and lifestyle-related factors, makes diagnosis, treatment, and prevention particularly challenging. Advances in understanding the underlying pathophysiological mechanisms of this disease have driven the development of new therapeutic that extend beyond the symptomatic relief provided by conventional treatments, namely acetylcholinesterase inhibitors and memantine. Emerging therapies aim to interfere with key biological processes of pathology, such as amyloid-β peptide deposition, tau protein dysfunction, neuroinflammation, among others, with the goal of modifying disease progression. The approval of three anti-amyloid monoclonal antibodies — aducanumab, lecanemab, and donanemab — by regulatory agencies such as the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) paves the way for the development of additional disease-modifying therapies, while reinforcing and encouraging research efforts towards more effective and durable strategies. This monograph discusses the pathophysiology of the disease, current diagnostic techniques, and the latest therapeutic advances. It also addresses the most promising clinical trials, future perspectives, and key challenges associated with the development and implementation of new drugs for the treatment of Alzheimer’s disease.
Alzheimer’s Disease is the most prevalent neurodegenerative disorder worldwide, accounting for 60 to 80% of dementia cases. Its complex and multifactorial etiology, involving a combination of genetic, environmental, and lifestyle-related factors, makes diagnosis, treatment, and prevention particularly challenging. Advances in understanding the underlying pathophysiological mechanisms of this disease have driven the development of new therapeutic that extend beyond the symptomatic relief provided by conventional treatments, namely acetylcholinesterase inhibitors and memantine. Emerging therapies aim to interfere with key biological processes of pathology, such as amyloid-β peptide deposition, tau protein dysfunction, neuroinflammation, among others, with the goal of modifying disease progression. The approval of three anti-amyloid monoclonal antibodies — aducanumab, lecanemab, and donanemab — by regulatory agencies such as the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) paves the way for the development of additional disease-modifying therapies, while reinforcing and encouraging research efforts towards more effective and durable strategies. This monograph discusses the pathophysiology of the disease, current diagnostic techniques, and the latest therapeutic advances. It also addresses the most promising clinical trials, future perspectives, and key challenges associated with the development and implementation of new drugs for the treatment of Alzheimer’s disease.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2025, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
204205751 Doença de alzheimer Terapias modificadoras da doença β-amilóide Proteína tau Ensaios clínicos Mestrado integrado - 2025