Research Priorities and Future Directions
1 Cross-Condition Mechanism Validation
Which ME/CFS mechanisms need testing in which conditions:
| Mechanism | Priority Conditions for Testing | Plasma cell autoimmunity (daratumumab) |
|---|---|---|
| Long COVID, PTLDS, autoimmune diseases where rituximab failed | \(\beta\) 2-receptor desensitization | EDS-POTS-MCAS, dysautonomia, Long COVID |
| Tetrahydrobiopterin (BH4) dysregulation | EDS with OI, POTS, dysautonomia, migraine | WASF3/ER stress pathway |
| Primary mitochondrial disorders, metabolic myopathies | NAD+ depletion | Cancer-related fatigue, aging-related decline, neurodegenerative disease |
| Glymphatic clearance failure | Alzheimer’s, Parkinson’s, migraine, TBI | GPCR autoantibody-monocyte reprogramming |
| Long COVID, autoimmune conditions with functional symptoms |
2 Biomarker Validation Across Conditions
The Heng 2025 7-biomarker panel (91% diagnostic accuracy in ME/CFS) includes:
- Immune: IL-8, TNF-\(\alpha\)
- Vascular: VWF, fibronectin, thrombospondin
- Metabolic: Lactate, pyruvate Research priority: Validate this panel in Long COVID, fibromyalgia, EDS-POTS-MCAS, and other conditions with multi-system dysfunction.