Metabolomic and Chronic Fatigue Syndrome – by Robert Naviaux, MD

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naviaux's explanationTesting an Exciting New Technology for Diagnosis and Management of ME/CFS and Other Illnesses

We are excited to work with the Open Medicine Foundation (OMF) to help blaze a new trail in ME/CFS research. Dr. Robert Naviaux and his team at the University of California, San Diego recently completed a metabolomics study of over 80 patients with ME/CFS and normal controls in collaboration with Dr. Eric Gordon and his team in northern California.

The results showed that there was a chemical signature in ME/CFS that might ultimately be used to help physicians diagnose and treat the disease.

The results were so exciting that we have now launched a validation study in a completely independent group of over 100 patients (already chosen and ready to go) with ME/CFS and controls from across the US and Canada. This study will be done in collaboration with Dr. Paul Cheney and Dr. Gordon’s team. A grant from OMF will make this next study possible.

OMF is leading the way to new hope for every patient with complex chronic diseases by collaborating with world-renowned, creative scientists to help search for the molecular causes that underlie the myriad of diverse symptoms. Progress is being made on many fronts. In just a year from now, we should have the science to add NextGen metabolomics to the tool kit needed to crack the mystery of ME/CFS.

Mitochondria – “Mitochondria” is not quite a household word, but when it comes to understanding complex chronic disease, it should be. Mitochondria are the hub of the wheel of metabolism.

More than 90% of the pathways that break down food into building blocks and 70% of the pathways that make new building blocks have at least one reaction that passes through mitochondria. These little bioreactors use the oxygen we breathe to turn food and drink into energy and to perform over 500 other important chemical reactions in the cell.

Mitochondria also have another key function: They stand guard over the cell, ready to defend it when things go wrong. When a virus attacks, or a toxin is detected, mitochondria stop what they were doing, change their shape and cellular locations, and take up arms to help defend the cell. Mitochondria then send messages in the form of metabolites to the nucleus of the cell and to neighboring cells to signal the danger so gene expression can be changed and neighboring cells can prepare for battle. Different signals are sent when the danger has passed to alert the cell that healing can proceed.

Recent scientific discoveries in our lab have shown that several different chronic complex diseases can result when this “cell danger response” (CDR) gets stuck in the “on” position for too long. When the CDR gets stuck, normal healing can’t proceed.  If this happens, it could theoretically lead to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Metabolomics – Metabolomics is one of the hottest rising stars in the high tech race to gain a molecular understanding of health and disease. Metabolomics uses a machine called a “mass spectrometer” to measure hundreds of chemicals in our blood.

In our lab, at the University of California San Diego, with a single blood specimen, we can measure over 500 of these chemicals from over 60 different biochemical pathways.

These chemicals are the building blocks that cells use to grow and function, to fight and to heal. Like a Hubble telescope for medicine, metabolomics is allowing us to see deeper and with greater clarity into the universe of the cell than has ever been possible before. In a drop of blood, we can “eavesdrop” on the collective conversations of all the cells in the body.

In ME/CFS, as in many complex chronic diseases, many genes interact with many environmental factors encountered at times of vulnerability. Complex diseases are not predestined by our genes alone. Complex diseases are ecogenetic—resulting from the interaction of genes inherited from our ancestors and environmental factors we encounter in a lifetime. Our metabolism is the real-time readout of the gene-environment interaction. Metabolomics is a new lens that allows us to “see” this inner world of the cell in a new way that lends itself to scientific discovery.

This new vision is leading to breakthroughs in our understanding of why patients with ME/CFS get stuck in a cycle of pain and suffering and disability. But more importantly, metabolomics is also shedding light on how rational therapies designed to trigger a return to health might be just around the corner.

 
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