Signals in the Flow: Vascular Biomarkers and Neurovascular Dysfunction in ME/CFS

Prof. Dr. Alain Moreau talked about research efforts to unveal biomarkers for vascular and neurovascular dysfunction in ME/CFS, to better stratify patients and guide precision medicine. By using a deep phenotyping protocol, his research group applied different digital technologies and combined them with omics analyses. By using the Hexoskin Smart Vest device, for example, they measured different physiological parameters as well as cerebral and peripheral oxygenation in a real-world setting, including brain oximetry during a stress test using non-invasive near infrared spectroscopy. Additional tests included cognitive assessments at baseline and 90 minutes as well as five days after stress induction. Notably, the team undertook home visits to also conduct tests in severely affected patients. To look for biological signals that may enable the development of biomarkers, the group also analyses bio samples, including blood, urine, and saliva in combination with different omics technologies. Using cognitive tests in a state of induced post-exertional malaise (PEM), the group identified three cognitive trajectories in the investigated ME/CFS patients. In the most severeley affected patients, they identified a measurable decrease in oxygen extraction, as well as muscle weakness and pain. They went on to match the three identified clusters of cognitive symptom severity with haptoglobin, which modulates vascular stress response, as a correlating biological marker. The published results (external link) show that haptoglobin 1-1 (Hp1-1), Hp2-2 and Hp2-1 were found to be present, according to their biological impact, in the three clusters matching resilient to intermediate to most severe cognitive impairments. Prof. Dr. Moreau went on to outline a selection of drugs and supplements that could potentialy target the idenfied dysfunctions. More recently, the groups was able to identify brain derived neurotrophic factor (BDNF) as another molecule that may act as a signal of vascular pathology in ME/CFS, again corresponding to the identified three cognitive trajectories. Based on their overall findings, promising drug candidates would be those that help to reduce hemolysis, improve microcirculation, restore the energy metabolism of red blood cells, and attenuate oxidative stress.