This project aims to test the nitrogen hypothesis, which is that damaging, nitrogen-containing by-products of energy metabolism accumulate more readily in the cells of ME/CFS patients.
Of particular interest are the mitochondria and their role in energy production and resolution of the inflammation that is generated by muscular stress and exercise. It is both possible and even likely that clues for potential biomarkers for PEM will be revealed in these highly detailed studies.
We hypothesize that toxic nitrogen-containing by-products of energy metabolism accumulate more readily in the cells of ME/CFS patients. This accumulation, in turn, creates a cycle of energy generation to overcome a stressed state while generating more toxic nitrogen by-products in the process. We will also identify the compounds that can circumvent the production of toxic nitrogen by-products and release patients from this cycle.
To test this hypothesis, we will culture white blood cells in growth media with added nitrogen-labelled amino acids and measure the nitrogen-labelled by-products of energy metabolism. Cells from 30 ME/CFS patients and 20 age and sex-matched controls will be collected and processed at the Stanford Genome Technology Center and cultured for our nitrogen tracking experiment. These experiments will be conducted on blood cells directly from ME/CFS patients and cells cultured from ME/CFS patients.
To capture whether there is an ammonia accumulation in vivo, our best available option is observing the urine concentration of nitrogen-containing metabolites over a short time-course in which varying levels of physical/mental activity have occurred. The 30 ME/CFS patients and 20 sex-match control subjects from the above experiment will be required to provide all urine samples over 4 consecutive days (~20 samples per individual) while their exertion and heartbeat data is collected using wearable technology. Normally, most nitrogen by-products are converted to primary urea along with amino acids, peptides, creatine, creatinine, and polyamines.
In a pathological state, highly reactive, toxic nitrogen by-products are excreted in the urine as nitrate, nitrite, and ammonia. We will measure the ratios of healthy to pathological nitrogen metabolites in the urine and correlate this with the metadata activity.
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