A European platform for drug repurposing
For decades, therapies for complex diseases such as diabetes, cancer and cardiovascular disease have focused on managing symptoms rather than addressing root causes. Despite enormous investments in drug discovery, efficacy remains limited and many trials fail, leaving patients with no or imprecise medication. The REPO-TRIAL(opens in new window) project set out to overcome this roadblock. “Modern medicine still largely defines diseases by organs and symptoms,” explains project coordinator Harald Schmidt, professor of Pharmacology at Maastricht University(opens in new window). “But most disease mechanisms cut across organs requiring a systems medicine approach. If we want precise and curative therapeutics, we must identify and target those causal mechanisms.” To increase not only precision but also speed and safety, REPO-TRIAL combined this approach with drug repurposing, i.e. finding new uses for already registered drugs. This was achieved by two in silico trials and advanced biostatistics.
From organ silos to disease modules
A major obstacle in symptom-based drug therapy is variability in patient response. Drug efficacy can vary, as patients grouped under the same diagnosis may have fundamentally different underlying disease mechanisms. REPO-TRIAL addressed this by applying systems and network medicine approaches to redefine diseases at the level of causal protein–protein interaction networks (modules), often causing symptoms in more than one organ. Using in silico modelling, multi-omics integration and mechanistic biomarkers, the consortium identified such modules across conventional disease boundaries and diagnosed them in biobank samples. This let the team match pre-approved drugs to precisely identified patients, rather than broad diagnostic labels, allowing curative, precision therapy.
Precision-guided clinical validation
Through the project, computational discoveries were translated into clinical testing. REPO-TRIAL implemented trials for treatment of stroke and heart failure in stratified patient groups, to enhance precision and treat only those patients who benefit. As repurposed drugs already have established safety data, this can shorten development timelines and reduce risks compared with de novo drug discovery. “Our objective was not simply faster trials,” says Schmidt. “It was smarter trials – targeting the right patients with the right mechanism-based intervention.” The project also created standardised approaches for multinational drug‑repurposing trials, including how to validate biomarkers and how to coordinate with regulators. “These advances demonstrate that precision drug repurposing can be implemented within existing European frameworks,” notes Schmidt.
Starting a broader translational ecosystem
Methodological and operational advances in REPO-TRIAL were transferred and consolidated for open access within REPO4EU(opens in new window), a pan-European platform integrating computational network medicine, biobanking, biomarker development and clinical trial expertise. The goal is to create a continuous pipeline from disease module identification to rapid clinical validation of repurposed compounds. Project partners are now advancing plans for a European Research Infrastructure provisionally named REPOSYSTEM. The ambition is to institutionalise systems medicine and drug repurposing as a permanent European capability.
A structural shift in biomedical research
By extending the life cycle of existing medicines and aligning them with precise molecular mechanisms, the overall strategy – the ‘REPO approach’ – could reduce development costs, accelerate patient access and improve long-term outcomes. The team’s ambition is to induce a durable transformation in Europe’s healthcare systems, away from chronic symptom management towards mechanism-based, potentially curative intervention and ideally presymptomatic prevention. “With REPO-TRIAL as its scientific foundation, REPO4EU as its operational engine and REPOSYSTEM as its structural ambition, Europe is taking steps towards a new therapeutic paradigm,” adds Schmidt.
