Biological evidence and mechanism-based disease classification for the improved diagnosis, prognosis and treatment of ME/CFS
The funded project — submitted under the EU Horizon call HORIZON-HLTH-2025-01-DISEASE-07: Tackling high-burden for patients and under-researched medical conditions — sets out to advance the biomedical understanding of ME/CFS through a coordinated, multi-national research programme.
Research workstreams address the core pathophysiological mechanisms of ME/CFS: immune dysregulation, neurological involvement, autonomic dysfunction, and metabolic abnormalities — with a translational focus on identifying reproducible biomarkers and informing future treatment development.
The project is built on a patient-centred research philosophy. Patient representatives and advocacy organisations are integrated into governance, ensuring that research priorities and outcomes remain connected to the lived experience of ME/CFS.
Myalgic encephalomyelitis (ME) is a debilitating multisystem disease affecting up to 1% of the population, defined by post-exertional malaise, persistent fatigue, cognitive and neurological symptoms, and autonomic, endocrine, and immune dysfunction. Clinical heterogeneity and the absence of specific diagnostic tests lead to long delays in diagnosis, lack of effective therapies, and a socioeconomic burden exceeding €40 billion annually in Europe.
DISCOVER-ME will deliver the first clinically actionable, biologically validated stratification framework for ME. Through harmonised clinical phenotyping of 2,000 patients and multi-omics profiling of >900 samples from five European biobanks, the project will identify, validate, and prioritise biomarkers across (epi)genetic, immune, metabolic, neuroendocrine, and vascular domains — overcoming decades of fragmented, underpowered studies that have stalled progress.
Three innovations set DISCOVER-ME apart: (i) a robust biomarker discovery and validation pipeline; (ii) the first systems-level taxonomy of ME grounded in mechanistic disease drivers and supported by AI-assisted stratification; and (iii) open-access disease maps and digital twin models combining biological mechanisms with social and economic determinants of health, enabling in silico testing of therapeutic hypotheses — underpinning biomarker-guided clinical trials and precision drug repurposing.
Patient involvement is embedded throughout — from co-design of phenotyping tools to stratification frameworks and policy recommendations — ensuring lived experience informs all biomedical and computational outputs. With over 20 partners across a dozen countries in Europe and Canada, DISCOVER-ME starts a new phase in discovery for ME.
