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Contribution of the innovative medicines initiative for the scientific advances on Alzheimer’s disease
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A doença de Alzheimer (AD) afeta profundamente indivíduos, famílias e sociedade, pelo que o seu impacto e complexidade exige uma abordagem multifacetada e a Innovative Medicines Initiative (IMI) tem procedido a avultados investimentos na sua investigação. Até à data, a IMI financiou dezoito projetos relacionados à AD, nomeadamente, PharmaCog, EMIF, AETIONOMY, EBiSC, EPAD, PRISM, ADAPTED, AMYPAD, MOPEAD, PHAGO, ROADMAP, IMPRiND, EQIPD, IM2PACT, RADAR-AD, NEURONET, PRISM2 e EPND.
Esta dissertação teve como propósito compilar os resultados desses projetos, organizando-os em quatro pilares de investigação identificadas pela Agenda Estratégica da IMI (SRA): 1) Identificação de Alvos e Biomarcadores, 2) Paradigmas Inovadores de Ensaios Clínicos, 3) Medicamentos Inovadores e 4) Programas de Adesão Personalizados ao Paciente.
Este estudo é pertinente ao refletir a contribuição da IMI para o avanço e compreensão do Alzheimer, obtendo uma imagem mais abrangente e clarificadora dos projetos individuais e os benefícios da sua complementaridade. Em termos científicos a dissertação constitui um contributo para tornar mais visível os avanços do entendimento da patologia, tais como a identificação de biomarcadores e alvos terapêuticos, e a inovação em ferramentas de diagnostico, metodologias de ensaios clínicos e tecnologias de monitorização digital.
Concretamente, foi realizada uma revisão literária, utilizando dados provenientes dos websites oficiais dos projetos, comunicações com coordenadores e a base de dados CORDIS. Dos 1.371 artigos inicialmente identificados, 246 foram incluídos para análise.
Após a análise dos resultados foi possível verificar que, notavelmente, uma parte significativa da pesquisa focou-se no eixo de "Identificação de Alvos e Biomarcadores", com todas as recomendações aplicáveis da SRA sendo alcançadas por projetos como PharmaCog, AETIONOMY, EMIF, EPAD, PRISM, ADAPTED, AMYPAD, PHAGO, IMPRiND, IM2PACT, EPND, EBiSC, RADAR-AD, EQIPD, MOPEAD e PRISM2. Os esforços destes projetos conduziram a avanços significativos no entendimento da patologia da AD, ao revelarem uma complexa interação de mecanismos ligados à progressão da doença, incluindo patologias amiloide e tau, neuroinflamação, alterações da substância branca, distúrbios do sono e fatores metabólicos. Fatores que contribuem para a variabilidade da doença—como variações no gene APOE, outras variantes genéticas, idade e sexo—também foram estudados, sendo cruciais na progressão da AD. Esta complexidade destacou a necessidade de abordagens multifacetadas no diagnóstico e tratamento.
Adicionalmente, os projetos contribuíram para o aprimoramento do diagnóstico e monitorização por meio de novos biomarcadores e desenvolvimento de instrumentos, abrindo portas a novas terapias ao identificarem alvos terapêuticos promissores. Por fim, foram desenvolvidos modelos preditivos, ferramentas e recursos que melhoraram a transição das descobertas pré-clínicas para aplicações clínicas, aumentando a capacidade de estudar os mecanismos da AD, identificar alvos terapêuticos e apoiar o desenvolvimento de novos medicamentos.
Sob o eixo “Paradigmas Inovadores de Ensaios Clínicos”, as contribuições de projetos como EPAD, AMYPAD, PRISM e RADAR-AD ajudaram na inovação do design de ensaios clínicos, na otimização de técnicas de neuroimagem e na adoção de endpoints digitais.
Projetos como PharmaCog, AETIONOMY, PHAGO, IMPRiND e IM2PACT avaliaram os benefícios de diferentes estratégias terapêuticas sob o eixo “Medicamentos Inovadores”, inclusive medicamentos reaproveitados, suplementos dietéticos e técnicas mais avançadas como a imunoterapia.
Finalmente, sob o eixo “Programas de Adesão Personalizados ao Paciente” os esforços de projetos como MOPEAD, RADAR-AD, EPAD e ROADMAP, concentraram-se no desenvolvimento de estruturas para rastreio proativo, na colaboração entre profissionais de saúde e aperfeiçoamento de métodos para apoiar a adesão à medicação e gerir fatores de risco.
A nossa análise demonstrou que os projetos da IMI contribuíram substancialmente para o avanço do conhecimento sobre o Alzheimer, fomentando a inovação em diagnósticos, desenvolvimento de tratamentos e cuidados ao paciente. Neste âmbito é ainda discutido o potencial de uma integração coordenada dos projetos que impulsionaria o impacto de cada projeto na pesquisa da doença. Ao abordar colaborativamente os desafios complexos da DA—desde os mecanismos moleculares até aos cuidados ao paciente—estes projetos aprimoram a compreensão, facilitam a deteção precoce e promovem intervenções oportunas. Esta abordagem global não só informa as políticas de saúde e acelera descobertas terapêuticas, mas também melhora significativamente os resultados para os pacientes.
Persistem, no entanto, desafios na otimização entre projetos e o envolvimento dos pacientes no processo de investigação. A NEURONET, um dos projetos, destacou estas questões e forneceu recomendações para colmatar as lacunas entre a IMI e a sua sucessora, a Iniciativa de Saúde Inovadora (IHI).
A doença de Alzheimer apresenta-se, como já mencionamos, uma patologia complexa onde a integração de saberes, experiências e necessidades é fundamental. Nesta dissertação ficou visível como a IMI, uma parceria público-privada, consegue, pela natureza dos esforços conjuntos dos stakeholders, avanços no entendimento e cuidados a ter com os pacientes.
Numa perspetiva de futuro parece-nos que esta dissertação pode encorajar análises posteriores que abranjam outros critérios de investigação tal como pode ser um ponto referenciador de iniciativas sucessoras da IMI.
Alzheimer's disease (AD) profoundly affects individuals, families, and society, necessitating a multifaceted approach due to its impact and complexity. The Innovative Medicines Initiative (IMI) has made significant investments in AD research. To date, the IMI has funded eighteen projects related to AD, including PharmaCog, EMIF, AETIONOMY, EBiSC, EPAD, PRISM, ADAPTED, AMYPAD, MOPEAD, PHAGO, ROADMAP, IMPRiND, EQIPD, IM2PACT, RADAR-AD, NEURONET, PRISM2, and EPND. This dissertation aimed to compile the results of these projects, organizing them into four research pillars identified by the IMI Strategic Research Agenda (SRA): (1) Target and Biomarker Identification, (2) Innovative Clinical Trial Paradigms, (3) Innovative Medicines, and (4) Patient-Tailored Adherence Programs. This study is pertinent as it reflects the IMI's contribution to advancing and understanding Alzheimer's disease, providing a more comprehensive and clarifying overview of individual projects and the benefits of their complementarity. Scientifically, the dissertation contributes to highlighting advances in understanding this pathology, such as the identification of biomarkers and therapeutic targets, and innovations in diagnostic tools, clinical trial methodologies, and digital monitoring technologies. Specifically, a literature review was conducted using data from the official websites of the projects, communications with coordinators, and the CORDIS database. Of the 1,371 articles initially identified, 246 were included for analysis. Upon analysing the results, it was noted that a significant portion of the research focused on the "Target and Biomarker Identification" axis, with all applicable SRA recommendations achieved by projects such as PharmaCog, AETIONOMY, EMIF, EPAD, PRISM, ADAPTED, AMYPAD, PHAGO, IMPRiND, IM2PACT, EPND, EBiSC, RADAR-AD, EQIPD, MOPEAD, and PRISM2. The efforts of these projects led to significant advances in understanding the pathology of AD by revealing a complex interaction of mechanisms linked to disease progression, including amyloid and tau pathologies, neuroinflammation, white matter changes, sleep disturbances, and metabolic factors. Factors contributing to disease variability—such as variations in the APOE gene, other genetic variants, age, and sex—were also studied, being crucial in AD progression. This complexity highlighted the need for multifaceted approaches in diagnosis and treatment. Additionally, the projects contributed to improving diagnosis and monitoring through new biomarkers and the development of instruments, opening doors to new therapies by identifying promising therapeutic targets. Predictive models, tools, and resources were developed that improved the transition from preclinical discoveries to clinical applications, enhancing the ability to study AD mechanisms, identify therapeutic targets, and support the development of new medications. Under the "Innovative Clinical Trial Paradigms" axis, contributions from projects such as EPAD, AMYPAD, PRISM, and RADAR-AD facilitated innovation in clinical trial design, optimization of neuroimaging techniques, and adoption of digital endpoints. Projects like PharmaCog, AETIONOMY, PHAGO, IMPRiND, and IM2PACT evaluated the benefits of different therapeutic strategies under the "Innovative Medicines" axis, including repurposed drugs, dietary supplements, and advanced techniques such as immunotherapy. Finally, under the "Patient-Tailored Adherence Programs" axis, efforts from projects such as MOPEAD, RADAR-AD, EPAD, and ROADMAP focused on developing frameworks for proactive screening, enhancing collaboration among healthcare professionals, and improving methods to support medication adherence and manage risk factors. Our analysis demonstrated that the IMI projects have substantially contributed to advancing knowledge about Alzheimer's disease, fostering innovation in diagnostics, treatment development, and patient care. In this context, we discuss the potential of coordinated integration of these projects, which would amplify the impact of each project on disease research. By collaboratively addressing the complex challenges of AD—from molecular mechanisms to patient care—these projects enhance understanding, facilitate early detection, and promote timely interventions. This comprehensive approach not only informs health policies and accelerates therapeutic discoveries but also significantly improves patient outcomes. Challenges persist, however, in optimizing collaboration among projects and involving patients in the research process. NEURONET, one of the projects, highlighted these issues and provided recommendations to bridge the gaps between the IMI and its successor, the Innovative Health Initiative (IHI). Alzheimer's disease presents itself, as we have already mentioned, as a complex pathology where the integration of knowledge, experiences, and needs is fundamental. In this dissertation, it became evident how the IMI, a public-private partnership, through the nature of the joint efforts of stakeholders, achieves advances in understanding and caring for patients. From a future perspective, we believe that this dissertation may encourage further analyses that encompass other research criteria and serve as a reference point for successor initiatives to the IMI.
Alzheimer's disease (AD) profoundly affects individuals, families, and society, necessitating a multifaceted approach due to its impact and complexity. The Innovative Medicines Initiative (IMI) has made significant investments in AD research. To date, the IMI has funded eighteen projects related to AD, including PharmaCog, EMIF, AETIONOMY, EBiSC, EPAD, PRISM, ADAPTED, AMYPAD, MOPEAD, PHAGO, ROADMAP, IMPRiND, EQIPD, IM2PACT, RADAR-AD, NEURONET, PRISM2, and EPND. This dissertation aimed to compile the results of these projects, organizing them into four research pillars identified by the IMI Strategic Research Agenda (SRA): (1) Target and Biomarker Identification, (2) Innovative Clinical Trial Paradigms, (3) Innovative Medicines, and (4) Patient-Tailored Adherence Programs. This study is pertinent as it reflects the IMI's contribution to advancing and understanding Alzheimer's disease, providing a more comprehensive and clarifying overview of individual projects and the benefits of their complementarity. Scientifically, the dissertation contributes to highlighting advances in understanding this pathology, such as the identification of biomarkers and therapeutic targets, and innovations in diagnostic tools, clinical trial methodologies, and digital monitoring technologies. Specifically, a literature review was conducted using data from the official websites of the projects, communications with coordinators, and the CORDIS database. Of the 1,371 articles initially identified, 246 were included for analysis. Upon analysing the results, it was noted that a significant portion of the research focused on the "Target and Biomarker Identification" axis, with all applicable SRA recommendations achieved by projects such as PharmaCog, AETIONOMY, EMIF, EPAD, PRISM, ADAPTED, AMYPAD, PHAGO, IMPRiND, IM2PACT, EPND, EBiSC, RADAR-AD, EQIPD, MOPEAD, and PRISM2. The efforts of these projects led to significant advances in understanding the pathology of AD by revealing a complex interaction of mechanisms linked to disease progression, including amyloid and tau pathologies, neuroinflammation, white matter changes, sleep disturbances, and metabolic factors. Factors contributing to disease variability—such as variations in the APOE gene, other genetic variants, age, and sex—were also studied, being crucial in AD progression. This complexity highlighted the need for multifaceted approaches in diagnosis and treatment. Additionally, the projects contributed to improving diagnosis and monitoring through new biomarkers and the development of instruments, opening doors to new therapies by identifying promising therapeutic targets. Predictive models, tools, and resources were developed that improved the transition from preclinical discoveries to clinical applications, enhancing the ability to study AD mechanisms, identify therapeutic targets, and support the development of new medications. Under the "Innovative Clinical Trial Paradigms" axis, contributions from projects such as EPAD, AMYPAD, PRISM, and RADAR-AD facilitated innovation in clinical trial design, optimization of neuroimaging techniques, and adoption of digital endpoints. Projects like PharmaCog, AETIONOMY, PHAGO, IMPRiND, and IM2PACT evaluated the benefits of different therapeutic strategies under the "Innovative Medicines" axis, including repurposed drugs, dietary supplements, and advanced techniques such as immunotherapy. Finally, under the "Patient-Tailored Adherence Programs" axis, efforts from projects such as MOPEAD, RADAR-AD, EPAD, and ROADMAP focused on developing frameworks for proactive screening, enhancing collaboration among healthcare professionals, and improving methods to support medication adherence and manage risk factors. Our analysis demonstrated that the IMI projects have substantially contributed to advancing knowledge about Alzheimer's disease, fostering innovation in diagnostics, treatment development, and patient care. In this context, we discuss the potential of coordinated integration of these projects, which would amplify the impact of each project on disease research. By collaboratively addressing the complex challenges of AD—from molecular mechanisms to patient care—these projects enhance understanding, facilitate early detection, and promote timely interventions. This comprehensive approach not only informs health policies and accelerates therapeutic discoveries but also significantly improves patient outcomes. Challenges persist, however, in optimizing collaboration among projects and involving patients in the research process. NEURONET, one of the projects, highlighted these issues and provided recommendations to bridge the gaps between the IMI and its successor, the Innovative Health Initiative (IHI). Alzheimer's disease presents itself, as we have already mentioned, as a complex pathology where the integration of knowledge, experiences, and needs is fundamental. In this dissertation, it became evident how the IMI, a public-private partnership, through the nature of the joint efforts of stakeholders, achieves advances in understanding and caring for patients. From a future perspective, we believe that this dissertation may encourage further analyses that encompass other research criteria and serve as a reference point for successor initiatives to the IMI.
Descrição
Tese de mestrado, Regulação e Avaliação do Medicamento e Produto de Saúde, 2025, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
Innovative medicines initiative Alzheimer's disease Personalized medicine Neurodegeneration Teses de mestrado - 2025