Health rising blog article by Cort Johnson, 21 April: An Eye on “The Mitochondria Man” : Robert Naviaux and Chronic Fatigue Syndrome (ME/CFS)
This is the start of an “Eye On” series focusing on researchers new to the chronic fatigue syndrome/fibromyalgia research fields. Few researchers present more exciting possibilities for ME/CFS than Dr. Robert Naviaux at UC San Diego (UCSD).
Naviaux recently joined the Scientific Advisory Board of the Open Medicine Foundation (OMF) and he’s believed to have co-authored a paper that is under review. Early reports suggest the Severe Patient Big Data study may, in its early stages, uncovered significant about the mitochondria in ME/CFS
In some ways Naviaux seems tailor-made for ME/CFS. Naviaux runs the Robert Naviaux Laboratory at UC San Diego, is the founder/ co-director of UCSD’s Mitochondrial and Metabolic Disease Center, and co-founder and a former president of the Mitochondrial Medicine Society. This man is clearly a pioneer in the relatively new and emerging field of mitochondrial research but he has an interesting immune side as well.
Naviaux trained at the NIH in tumor immunology and natural killer cell biology, and at the Salk Institute in virology and gene therapy. If ME/CFS or FM turns out to have a viral/inflammation/mitochondrial connection it’s hard to imagine someone better placed to take advantage of that.
Naviaux gained some renown in 2013 when he was able to reverse autism in a mouse model using a hypothesis that could help explain chronic fatigue syndrome and fibromyalgia as well. He proposed that a sustained “cell danger response” is causing the cells in autism to essentially to shut down, stop communicating with other cells and go into hibernation.
Naviaux believes that cells damaged by viruses, or toxins react defensively causing their membranes stiffen:
“When cells are exposed to classical forms of dangers, such as a virus, infection or toxic environmental substance, a defense mechanism is activated. This results in changes to metabolism and gene expression, and reduces the communication between neighboring cells. Simply put, when cells stop talking to each other, children stop talking.” Naviaux
(That’s an intriguing idea given the evidence of “immune exhaustion” in ME/CFS and FM, and the rather massive alterations of immune cell networks Gordon Broderick and Dr. Klimas have found in ME/CFS. Could immune cell shut downs be behind those network alterations? )
Everybody seems to believe that the innate or early immune response which causes inflammation is involved in ME/CFS but Naviaux has taken the conversation a step further by tying in the mitochondria. Naviaux knew the mitochondria were involved in inflammation – they can be huge emitters of free radicals – and looked for ways in which they interacted with the immune system. He found them in substances called “mitokines” such as ATP and adenosine that cells with distressed mitochondrial emit.
The purines and pyrimidines ( ATP, ADP, UTP, and UDP), produced by these damaged cells can effect everything from inflammation, neurotransmission, pain production, and autonomic nervous system activity. They bind to purinergic and other receptors on cells found from the circulatory to digestive to immune systems to the brain.
Sleeping Sickness Drug
Naviaux used a drug called suramin that battled sleeping sickness to reverse autism in his mouse model. An anti-purinergic signaling drug, suramin, Naviaux believes, stops the cell danger signal in its tracks. In two studies he’s been able to show that the drug rebuilt the mouse’s brain synapses, re -enabled stalled cell-to-cell signaling, improved its social behavior and motor coordination and normalized it’s mitochondrial metabolism. The drug is now being tested in a small trial of autistic children.
Cascade-stop.jpg Suramin is more of use for what it reveals than as a treatment possibility than a full-flung treatment. It can only be taken for couple of months but newer antipurinergic medicines might be able to be taken for longer or might just need to be taken intermittently.
As Naviaux developed his hypothesis that damaged cells are triggering purinergic signaling cascades in autism, Donald Staines in Australia was proposing vasoactive neuropeptides were doing much the same thing in ME/CFS. Staines also proposed that ATP and adenosine releases from cells with mitochondrial problems may be causing the purinergic signaling to go bananas in ME/CFS.
Meanwhile Alan Light’s examination of physiological pathways linked to stress and distress in ME/CFS was uncovering issues with purinergic signaling as well. Light found that increased purinergic receptor activity was highly associated with post exertional fatigue after exercise in ME/CFS (but not MS). He, too, suggested that purinergic receptors in ME/CFS patients were reacting to ATP molecules emanating from stressed cells. Back in 2012 he proposed that purinergic receptor upregulation in ME/CFS was turning the microglia in the brain on and producing pain and fatigue in ME/CFS.
Naviaux and other ME/CFS researchers, then, may be coming from different directions and ending up in much the same place.
We don’t know what Naviaux has found in ME/CFS – we’re waiting on his publication for that; it could be something entirely different but his past research alone suggests that he is someone to watch.
A member of the Health Rising Forums, Rachel Riggs, knows this first hand. After visiting Dr. Naviaux’s lab she described a researcher who was very enthusiastic about ME/CFS, who mentioned linkages between autism and the disease – a disease, he thought, which put ME/CFS bodies in a kind of hibernation. Dr. Naviaux said his paper on ME/CFS will, if and when it is published, surprise a lot of people. Rachel had a palpable sense that the lab was on the cusp of something big.
Naviaux’s got some big accomplishments behind him and some big toys to play with. His lab developed two advanced technologies; biocavity laser spectroscopy and mtDNA mutation detection by mass spectrometry, and recently created new bioinformatic methods that allow them to better analyze genetic data. Put all that together and Naviaux says he has the ability to “dissect the metabolic and molecular features of virtually any disease”.
Naviaux appears to be all in ME/CFS. His biggest hurdle may be finding the money to fully study it. Hopefully the new approach by the NIH or the growing ability of ME/CFS donors to support exciting research will be enough.
Naviaux is part of an increasing focus on the mitochondria in ME/CFS research circles. The Chronic Fatigue Initiative has engaged Maureen Hanson to do a series of ME/CFS mitochondrial studies. Richard Deth, a mitochondrial expert, is working with Dr. Klimas at the Institute for Neuroimmune Institute in Florida. Dr. Saligan, a P2P report participant, and member of the NIH Intramural study is a bit of a wild card. His work on the stress response and catastrophizing has raised concerns, but his main research interest is focused on the physiological aspects of cancer fatigue.
Saligan has done studies on murine models of radiation induced fatigue, gene expression and cancer fatigue, prostate cancer and fatigue, inflammation and cancer fatigue, BDNF and fatigue, immunogenomic markers and fatigue, mitochondria and prostate fatigue, biomarkers and cancer fatigue and on and on and he’s done one review on catastrophizing and fatigue.
