This project aims to understand the origin of postural orthostatic tachycardia syndrome (POTS).
Aspects of this PLF are highly consistent with mechanisms that result in POTS and post-exertional malaise (PEM), which are seen in many ME/CFS patients. These proposed studies offer significant opportunities for the identification of new drug targets and drug therapies for ME/CFS.
POTS is one of the more common symptoms of ME/CFS. This syndrome appears to involve the cardiopulmonary and peripheral vascular systems, both are modulated by the autonomic nervous system. It is unclear why these systems become dysfunctional to cause POTS but understanding the biological pathology underlying it will be relevant to helping understand its relationship to ME/CFS.
Cardiopulmonary exercise testing together with direct measurement through invasive arterial catheters (iCPET) has been useful to define the reason for unexplained dyspnea in general populations thought to be heart or lung in origin. Using this same diagnostic tool, ME/CFS patients have been evaluated and found to demonstrate a preload failure (PLF) pattern under maximum exercise. There are two forms of this PLF that has been observed: low flow and high flow. The low flow phenotype appears to be consistent with a failure of the autonomic nervous system to shift blood from the venous to the arterial side of the circulation or another possibility is a reduced total blood volume. On the other hand, the high flow phenotype appears as an arterial to venous shunt in the peripheral circulation or another possibility is a reduced oxygen delivery to peripheral circulatory beds or a reduced utilization by the mitochondria.
A blood tissue repository has been underway at the BWH for ME/CFS patients undergoing iCPET for many years and blood is available to study 84 ME/CFS patients (all with POTS) and 30 healthy participants for comparison. These blood samples are obtained before, during peak, and one hour after an iCPET procedure and will undergo analysis by proteomic, phospho-proteomic, and metabolomic methods.
Phospho-proteomics is an analysis form yet to be conducted on ME/CFS patient samples. Plasma proteomics have been conducted in ME/CFS patients but always at rest and not under stress exercise conditions when fatigue and exercise-induced differences are most likely to become evident.
Averting a second pandemic:
Open Medicine Foundation leads groundbreaking international study of
Long COVID’s conversion to ME/CFS
AGOURA HILLS, CALIF. — Open Medicine Foundation (OMF) is leading a large-scale international collaborative study investigating the potential conversion of Post-Acute Sequelae SARS-CoV-2 infection — more commonly known as Long COVID or Post-COVID Syndrome — to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a chronic, life-altering disease with no known cause, diagnostic test or FDA approved treatments available.
Up to 2.5 million people in the U.S. alone suffer from ME/CFS; the COVID-19 pandemic could at least double that number. An estimated 35 percent of Americans who had COVID-19 have failed to fully recover several months after infection, prompting many to call it “a potential second pandemic.”
OMF recognized a familiar health crisis emerging, one with eerie similarities to ME/CFS. This crisis presented a unique opportunity to understand how a viral infection — in this case COVID-19 — may develop into ME/CFS in some patients. The goal is to find targeted treatments for ME/CFS patients and ultimately prevent its onset in people infected with SARS-CoV-2 or other infections.
The federal government is only now investing in Post-COVID research, with no focus on its connection to ME/CFS. OMF has already engaged researchers for the largest-scale study of its kind, solely supported by private donors who have contributed over one million dollars to date. When fully funded, the five million dollar, three-year study will be conducted across the globe at OMF funded Collaborative Research Centers, led by some of the world’s top researchers and ME/CFS experts.
In a significant percentage of patients, infections preceded their development of ME/CFS. For example, according to the CDC about one in ten infected with Epstein-Barr virus, Ross River virus, or Coxiella burnetti develop symptoms that meet the criteria for ME/CFS.
The ability to follow the development of ME/CFS from a known viral infection is unprecedented to date and crucial to researchers’ understanding of the disease. The focus of this study is to find the biological differences between persons returning to good health after COVID-19 and persons who remained ill more than six months after infection and developed ME/CFS. Understanding these alterations in key pathways can lead to groundbreaking discoveries including new biomarkers, drug targets, and prevention and treatment strategies.
About Open Medicine Foundation
Established in 2012, Open Medicine Foundation leads the largest, concerted worldwide nonprofit effort to diagnose, treat, and prevent ME/CFS and related chronic, complex diseases such as Post Treatment Lyme Disease Syndrome, Fibromyalgia, and Post COVID. OMF adds urgency to the search for answers by driving transformational philanthropy into global research. We have raised over $28 Million from private donors and facilitated and funded the establishment of five prestigious ME/CFS Collaborative Research Centers around the world. To learn more, visit www.omf.ngo.
Heather Ah San
Development and Communications Manager