“Hopefully this will finally make people change their attitudes to this disease.” Dr. Judy Mikovits
The news had been in the air for the last week; the Whittemore Peterson Institute was going to publish something big – really big – on Friday. Then early Thursday the news was out – a retrovirus had been found in many if not almost all ME/CFS patients. The media had prepared themselves well – feature stories shot up on the Wall Street Journal, LA Times, NPR, Scientific American, etc.
It was big news indeed – after two decades chronic fatigue syndrome (ME/CFS) was back in the news in a big way. Ironically the last big splash like this in the 1990’s featured a retrovirus in ME/CFS that didn’t pan out and left a young researchers career in tatters. One has the feeling that that is not going to happen this time.
A Deep Bench – One reason is the extraordinary depth of the research team involved in these findings. It’s not often that the head of the NCI’s AIDS and Viral Cancer Center of Excellence has any reason to utter the words “chronic fatigue syndrome” to the national media. But here was Dr. Stuart Le Grice not only uttering the words but likening this stage of the fight to the early HIV epidemic and its partners pledging the National Cancer Institutes best at unraveling just what is going on.
“NCI is responding like it did in the early days of HIV,” says Stuart Le Grice, head of the Center of Excellence in HIV/AIDS and cancer virology at NCI and one of the organizers of the July workshop.
Besides Dr. Grice (not an author of the study) we had Dr. Ruscetti from the National Cancer Institute and the discoverer of XMRV, Dr. Silverman from the Cleveland Clinic chiming in. Clinic. To top it off the study was published in Science, the most prestigious and oft cited scientific journal in the world – an extraordinary event for the ME/CFS research community.
“These compelling data allow the development of a hypothesis concerning a cause of this complex and misunderstood disease, since retroviruses are a known cause of neurodegenerative diseases and cancer in man,” Francis Ruscetti, Ph.D., Laboratory of Experimental Immunology, NCI.
The Big Picture – ME/CFS patients have never seen anything like this. And in fact it isn’t all about them. Among the stranger findings emanating out of the Whittemore Peterson Institute is the fact that this retrovirus, which had heretofore been associated only with prostate cancer in some neurological diseases was founded on most 4% of the healthy controls blood. This suggests that about 10 million Americans could be carrying a ticking bomb. It also suggests that anyone who’s having a blood transfusion could be at risk. Those two things got enough of the National Cancer Institute’s attention that it quickly convened a workshop in August on how to deal with this problem.
The study released by the Whittemore Peterson Institute found that two thirds of chronic fatigue syndrome (ME/CFS) patients were carrying a recently discovered retrovirus called XMRV that is associated with severe cases of prostate cancer. They were lead to this discovery by the fact that both ME/CFS and prostrate cancer patients often have a dysfunction in an important immune enzyme called RNase L. When they looked at the ME/CFS patients they were astonished to find that most of them carried the virus as well.
In fact the prevalence of this virus in ME/CFS may have been understated. In telephone calls Dr. Mikovits reported that the WPI was finding antibodies to the retrovirus in fully 95% of their ME/CFS samples. The fact that the few fibromyalgia patients tested also tested positive for the virus suggests that it may be found in other neuro- immune diseases and the WPI will be testing that possibility.
“I can’t wait to be able to tell my patients. It’s going to knock their socks off” Dr. Judy Mikovits
The New (Old) AIDS – AIDS and chronic fatigue syndrome were often mentioned together earlier in our diseases history. The infectious onset , the chronic course, the devastating nature of the illness, the inability to identify a pathogen and the fact that HIV had just arrived on the scene as well – all made both lay and professional people think ‘retrovirus’. Twenty five years later the WPI is asserting that, yes, ME/CFS patients are infected with a retrovirus – in fact, one of only three human infectious retroviruses in existence. In some ways it fits very well; all retroviruses disrupt the immune system in such a way as to allow other viruses to flourish. Several studies have, of course, found highly increased rates of opportunistic viral infections in ME/CFS – a common, though more devastating finding in AIDS.
The Long Road – But after the ill-fated Wistar retroviral finding (see Osler’s Web) the scientific community mostly begged off the viral hunt in ME/CFS. Part of the reason was just our bad luck. HIV was killing people by attacking the masterminds of the late immune response – the T- helper cells. T cells were and are a hot item in the medical research community. It’s the late immune response, after all, that is primarily responsible for finally knocking down a pathogen.
The early or innate immune response, on the other hand, is ‘merely’ responsible for identifying the pathogens and engaging in a holding action until the big guns (T-cells) come to the rescue. Its the natural killer cells in the early immune response that are primarily affected in chronic fatigue syndrome and they weren’t getting much respect. While they certainly kill invaders natural killer cells are also responsible for putting out the alert that a pathogen is present. AIDS wipes out T-helper cells, it may be that XMRV in ME/CFS patients knocks out natural killer cells; either way the immune fails to spot pathogen’s. AIDS and ME/CFS patients may suffer from a similar problem but in different parts of the immune system.
Once the innate immune response research got cranking it took some remarkable findings in the late 1990’s and the early 2000’s regarding the RNase L enzyme and ME/CFS to eventually to turn Dr. Mikovits head toward Dr. Silvermans work on XMRV. Science did work – just in a greatly delayed fashion.
Transmission – If the XMRV virus is the key to the viral cascade that the Whittemore Peterson Institute has identified in so many of its patients a central question involves how did that did that key get in the door? Viruses don’t just jump up and attack people they need to be transmitted. It’s clear that this virus is not spread through the air which means that in order to get infected with it the virus needs to be transmitted from human to human via the saliva, blood, semen or mother’s milk . Just how the virus gets transmitted and how easily it gets transmitted will surely be the one of the major questions the National Cancer Institute and the WPI will be working on.
Treatment – the list of possible treatments consists of anti-retroviral drugs that can have severe side effects. The WPI will apparently be testing these drugs out in some of their patients.
The Cause? – Nor do they know if it’s the cause of ME/CFS. Dr. Mikovits is clearly leaning towards that idea but the WPI is careful to state that that has not been proven. Until we know better the XMRV is simply another virus – albeit with intriguing possibilities – that has been found in ME/CFS patients. It will take much more study as well as independent verification of the WPI’s results before we can say how significant this virus is.
Game Changer – Only time will tell how significant this finding will end up being but it’s clearly already realigning the ME/CFS research playing field. Dr. Reeves stated that the CDC is already attempting to replicate the study findings. The National Cancer Institutes quickly convened workshop, the presence of this study in such a prominent medical journal, and the incredible news coverage that have accompanied these findings hopefully suggest that something fundamental has changed. Yes, there are questions about the results and they will be covered in a later blog, but the widespread interest in this study will surely translate into greatly increased funding for research into XMRV and hopefully into more immune research in chronic fatigue syndrome as well.
“This is going to create an avalanche of subsequent studies.” Dr. Schnaffer (Vanderbilt)
Regarding federal funding this study couldn’t have come at a better time. Neither the CDC nor the NIH (with the exception of NK cells) have show any interest in pathogens or the immune system in over 10 years. Research into ME/CFS has declined precipitously in both institutions over the past five years. Hopefully this study will shine a light on how poorly our federal government has funded ME/CFS research and open up much needed possibilities for research and treatment.
“The scientific evidence that a retrovirus is implicated in CFS opens a new world of possibilities for so many people,” said Annette Whittemore, founder and president of WPI and mother of a CFS patient. “Scientists can now begin the important work of translating this discovery into medical care for individuals with XMRV related diseases.”