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.
