Scheibenbogen et al. (2025)
- Authors: Carmen Scheibenbogen, Judith Bellmann-Strobl, Klaus J. Wirth
- Institutes: Charité – Universitätsmedizin Berlin, Berlin, Germany, Berlin Institute of Health (BIH), Berlin, Germany, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany
- Publisher: United States Patent and Trademark Office (USPTO)
- Link: DOI
Summary
This research highlights a significant shift toward addressing the vascular and circulatory roots of ME/CFS and Long COVID. By targeting the signaling pathways that control blood vessel dilation, the proposed treatment aims to break the cycle of oxygen deprivation and muscle damage that causes post-exertional malaise. If successful, this approach could provide one of the first evidence-based pharmacological treatments for the physical disability associated with these conditions.
What was researched?
This research explored the use of a soluble guanylate cyclase (sGC) stimulator, specifically vericiguat 💊, to treat chronic vascular dysfunction and impaired blood flow in patients with ME/CFS and Long COVID.
Why was it researched?
The study was motivated by the hypothesis that post-infectious syndromes involve endothelial dysfunction and a ‘vicious cycle’ where low blood flow leads to anaerobic metabolism, sodium/calcium overload, and mitochondrial damage in the muscles. Stimulating the sGC pathway is intended to restore proper blood vessel function and tissue oxygenation.
How was it researched?
The research is supported by the VERI-LONG/VERI-ME clinical trial, a Phase 2a double-blind, placebo-controlled study involving 104 participants aged 18 to 50. Participants received a titrated dosage of the drug over 10 weeks, and researchers measured changes in physical function using the SF-36 questionnaire alongside cardiovascular safety monitoring.
What has been found?
The patent and associated trial data indicate that sGC stimulation can effectively bridge endothelial dysfunction to improve microvascular perfusion. Preliminary results suggest that improving the bioavailability of nitric oxide-like signaling leads to a reduction in fatigue and an improvement in physical capacity. The treatment was generally well-tolerated when titrated slowly.
Discussion
A key finding is that the vascular disturbance persists long after the initial infection has cleared, acting as a primary driver of exercise intolerance. The study’s focus on younger and middle-aged adults (18-50) limits the current generalizability to older populations or children. Future analysis will need to determine the long-term sustainability of the improvements.
Conclusion & Future Work
Targeting the sGC/cGMP pathway with vericiguat represents a promising therapeutic strategy for treating the vascular components of ME/CFS. Further studies are recommended to integrate this vascular therapy with other immune-modulating treatments.