Periodic Reporting for period 2 - MIRIADE (Multi-omics Interdisciplinary Research Integration to Address DEmentia diagnosis)
Période du rapport: 2021-11-01 au 2024-08-31
Dementia is a threatening disease due to its increasing incidence in the aging population, bulging costs and inhumane clinical course, while no cure is currently available. To make progress in the development of effective drugs for dementia, there is an urgent need for body fluid biomarkers to enable precision health for different forms of dementia. The aim of MIRIADE was to train a new generation of scientists able to optimise and accelerate development of novel body fluid biomarkers for dementia.
MIRIADE had the following aims:
o To equip 15 scientists with unique skills and strategies to target biomarker development (WP6).
o To establish a roadmap for strong stakeholder interactions to accelerate the biomarker development process (WP1-5,7).
o To develop an open integrated data platform for biomarker development (WP1).
o To develop computational tools for rational prediction of biomarkers (WP1,2).
o To develop and validate novel biomarker assays for specific types of dementia (WP1-3).
o To facilitate clinical implementation of biomarker assays (WP4).
Conclusions: MIRIADE trained 15 specialised ESRs to optimise and accelerate development of novel dementia biomarkers through dedicated training programs, research activities and intersectoral collaboration (including secondments). In WP1, existing -omics data were integrated to identify candidate biomarkers, which has led as to the creation of an open database and a dementia disease map. WP2 concentrated on generating assays for several biomarkers, employing various technologies in parallel. This led to the successful generation of several novel robust assays. WP3 clinically validated the developed biomarkers, achieving positive results for several assays. WP4 further advanced these assays for market readiness, focusing on preanalytical stability and developing standard operating procedures (SOPs) for clinical use. WP5 analyzed workflows and collaboration across research groups, identifying bottlenecks and opportunities to improve biomarker development, with a focus on inter-group collaboration and data sharing and reuse practices.
MIRIADE had the following aims:
o To equip 15 scientists with unique skills and strategies to target biomarker development (WP6).
o To establish a roadmap for strong stakeholder interactions to accelerate the biomarker development process (WP1-5,7).
o To develop an open integrated data platform for biomarker development (WP1).
o To develop computational tools for rational prediction of biomarkers (WP1,2).
o To develop and validate novel biomarker assays for specific types of dementia (WP1-3).
o To facilitate clinical implementation of biomarker assays (WP4).
Conclusions: MIRIADE trained 15 specialised ESRs to optimise and accelerate development of novel dementia biomarkers through dedicated training programs, research activities and intersectoral collaboration (including secondments). In WP1, existing -omics data were integrated to identify candidate biomarkers, which has led as to the creation of an open database and a dementia disease map. WP2 concentrated on generating assays for several biomarkers, employing various technologies in parallel. This led to the successful generation of several novel robust assays. WP3 clinically validated the developed biomarkers, achieving positive results for several assays. WP4 further advanced these assays for market readiness, focusing on preanalytical stability and developing standard operating procedures (SOPs) for clinical use. WP5 analyzed workflows and collaboration across research groups, identifying bottlenecks and opportunities to improve biomarker development, with a focus on inter-group collaboration and data sharing and reuse practices.
Fifteen ESRs were trained on the complete biomarker development chain, including big data, entrepreneurship, regulatory affairs, patient involvement, and medical needs.
The training weeks focussed on novel biomarker detection technologies, writing grants and texts for lay audiences, entrepreneurship in science, regulatory affairs, project management, public-private partnership opportunities, antibody development and characterisation.
We integrated existing –omics data for identification of pathways and candidate biomarkers for differential dementia diagnosis (WP1). For each dementia type, the 3-5 most promising candidates have been prioritized for development in WP2 and 3 and developed an open source Online Dementia Disease map. In addition, we developed several prediction tools relevant for biomarker development, such as a tool to predict CSF presence of brain proteins.
The project generated several assays for the candidate biomarkers from WP1 that are common and specific for each dementia type using state-of-the-art protein technologies (WP2). Biomarkers were developed in parallel on different technologies (e.g. DDC, CRH, MOG), for optimal synergism, and comparison of the efficacies of each strategy to build a roadmap for optimised development in WP5.
Next, selected candidate biomarkers were clinically validated in biosamples (WP3). We assessed the clinical context of use and accuracies of biomarkers. The results showed positive clinical validation for several biomarkers, such as a multiplex SRM panel, improved pTau181 assay, AQP4, p-tau217&231, plasma Aβ42/40, p-tau231, Progranulin, oligomeric Neurofilament, Dopamine decarboxylase, and beta-synuclein.
Biomarker assays that were available on the market were evaluated for market entry, such as blood NfL, (p)Tau and Snap-25. Preanalytical stability was assessed to generate standard operating procedures (SOPs) for sample collection in clinical practise, and reference method development was started. Several relevant actions for market introduction have been started for the biomarker neurofilament light, including obtaining EMA approval, upscaling, and the development of alternative assay modalities, such point of care set-ups and alternative antibody-reagents.
A roadmap for innovation of the biomarker development process has been provided. This was done by studying the different assay development strategies (e.g. SRM vs. immunoassay development) focussing on a.o. communication, decision and interaction strategies) and by identifying hurdles and solutions for open (big) data sharing, to make collaborative biomarker research more effective. Based on the results, recommendations are presented in a roadmap of best practices for data and results sharing, reuse and integration.
Communication and dissemination of the project was led by the ESRs and main communication channels included the website and social media (X, LinkedIn, Instagram and YouTube). ESRs attended a multitude of congresses, with various scopes, from deep-dive into the project related subjects to broader clinical (dementia) conferences with a wider audience (including patient advocacy groups). Impactful papers were published by ESRs with the consortium. MIRIADE is proud to already have published XXXXX open access publications and achieved all main objectives despite the pandemic circumstances.
The training weeks focussed on novel biomarker detection technologies, writing grants and texts for lay audiences, entrepreneurship in science, regulatory affairs, project management, public-private partnership opportunities, antibody development and characterisation.
We integrated existing –omics data for identification of pathways and candidate biomarkers for differential dementia diagnosis (WP1). For each dementia type, the 3-5 most promising candidates have been prioritized for development in WP2 and 3 and developed an open source Online Dementia Disease map. In addition, we developed several prediction tools relevant for biomarker development, such as a tool to predict CSF presence of brain proteins.
The project generated several assays for the candidate biomarkers from WP1 that are common and specific for each dementia type using state-of-the-art protein technologies (WP2). Biomarkers were developed in parallel on different technologies (e.g. DDC, CRH, MOG), for optimal synergism, and comparison of the efficacies of each strategy to build a roadmap for optimised development in WP5.
Next, selected candidate biomarkers were clinically validated in biosamples (WP3). We assessed the clinical context of use and accuracies of biomarkers. The results showed positive clinical validation for several biomarkers, such as a multiplex SRM panel, improved pTau181 assay, AQP4, p-tau217&231, plasma Aβ42/40, p-tau231, Progranulin, oligomeric Neurofilament, Dopamine decarboxylase, and beta-synuclein.
Biomarker assays that were available on the market were evaluated for market entry, such as blood NfL, (p)Tau and Snap-25. Preanalytical stability was assessed to generate standard operating procedures (SOPs) for sample collection in clinical practise, and reference method development was started. Several relevant actions for market introduction have been started for the biomarker neurofilament light, including obtaining EMA approval, upscaling, and the development of alternative assay modalities, such point of care set-ups and alternative antibody-reagents.
A roadmap for innovation of the biomarker development process has been provided. This was done by studying the different assay development strategies (e.g. SRM vs. immunoassay development) focussing on a.o. communication, decision and interaction strategies) and by identifying hurdles and solutions for open (big) data sharing, to make collaborative biomarker research more effective. Based on the results, recommendations are presented in a roadmap of best practices for data and results sharing, reuse and integration.
Communication and dissemination of the project was led by the ESRs and main communication channels included the website and social media (X, LinkedIn, Instagram and YouTube). ESRs attended a multitude of congresses, with various scopes, from deep-dive into the project related subjects to broader clinical (dementia) conferences with a wider audience (including patient advocacy groups). Impactful papers were published by ESRs with the consortium. MIRIADE is proud to already have published XXXXX open access publications and achieved all main objectives despite the pandemic circumstances.
MIRIADE has trained 15 ESRs with excellent scientific skills and a strong network, who are able to apply the most advanced protein technologies combined with entrepreneurial mind-sets to successfully bring biomarkers to the clinic. Our developed blood and CSF biomarker tools (>10 CSF and blood assays, EMA letter of qualification for NfL) allow for precision medicine for dementia. The open access data-sources provide an unprecedented big data integration platform for candidate biomarker identification. The learning with respect to interactions between researchers, complexity of datasharing processes and their influences on project management will be considered in future project design, to optimize effectiveness of such projects.
Early detection of dementia –even before clinical symptoms arise- will have a major impact on the diagnosis and treatment of (future) dementia patients, especially now that treatments are being approved. Timely accurate diagnosis reduces the costs of the diagnostic process, and allows for early intervention leading to better quality of life and less societal costs. MIRIADE has provided a highly skilled workforce in a vital area of health care (dementia research) within Europe, and frameworks for biomarker development beyond this medical area. There is a clear opportunity for Europe to take a lead in the development of next generation biomarkers in dementia. The industrial partners have strengthened their position in the development of new dementia biomarkers.
Early detection of dementia –even before clinical symptoms arise- will have a major impact on the diagnosis and treatment of (future) dementia patients, especially now that treatments are being approved. Timely accurate diagnosis reduces the costs of the diagnostic process, and allows for early intervention leading to better quality of life and less societal costs. MIRIADE has provided a highly skilled workforce in a vital area of health care (dementia research) within Europe, and frameworks for biomarker development beyond this medical area. There is a clear opportunity for Europe to take a lead in the development of next generation biomarkers in dementia. The industrial partners have strengthened their position in the development of new dementia biomarkers.