The Symposium on Viruses in Chronic Fatigue Syndrome

Discussion in 'Fibromyalgia Main Forum' started by karinaxx, Aug 10, 2008.

  1. karinaxx

    karinaxx New Member

    This is worthwhile reading, even if it is long.
    There is new research on enteroviruses in there, about the mood disorder in ME/CFS/BIPOLAR and HHV-6 and a suggested new test for a biomarker on NKcells by N.Klima!!!!!!

    The Symposium on Viruses in Chronic Fatigue Syndrome (ME/CFS) (May, 2008): Part I
    by Cort Johnson

    Highlight on the HHV-6 Foundation

    The HHV-6 Foundation produced both the International Conference on HHV-6 & 7 and the International Symposium on Viruses and CFS in Baltimore, Md in May, 2008. The IACFS/ME co-sponsored the events. Financial Support was provided by the CFIDS Association of America, the Whittemore-Peterson Institute, PANDORA, ProHealth and others.
    One of the most impressive aspects of the Symposium was the people who put it on. Created just a few years ago ,and led by Kristin Loomis Executive Director and Scientific Director Dharam Ablashi - the HHV-6 Foundation is clearly on a mission to make a difference.

    The Foundation is constantly probing and cajoling researchers to examine the viral connections to disease. Many, perhaps most of the researchers presenting at the conference were indebted to the Foundation for assistance with materials or with direct testing. They assisted Birgitta Evengard and Kasuhiro Kondo with testing and persuaded others, such as Brigitte Huber to include HHV-6 in their studies. They played a major behind the scenes role in helping convince Roche to take on the Montoya/Valcyte study , funded significant parts of Stanford’s pre-trial efforts and lined up over a dozen outside collaborations for sophisticated testing.

    The HHV-6 Foundation embodies the kind of creative activity that the private sector can be so good at and it was heartening to see them at work.

    Finding ‘Waldo’: The Montoya Valcyte Chronic Fatigue Syndrome (ME/CFS) Study
    J. G. Montoya. A randomized, double-blind, placebo-controlled trial on the use of Valganciclovir in patients with chronic fatigue syndrome (CFS) and elevated human herpesvirus and Epstein-Barr virus antibodies.

    The Montoya team and Roche Pharmaceuticals have asked for some breathing room and the results from the Valcyte trial will not be provided here. Montoya presented some key results at the conference but he’s still in the middle of processing data that may affect how the study is perceived and he’s asked that the results not be posted wait until he’s finished.

    The HHV-6 Foundation’s financial and administrative assistance allowed Montoya to characterize his patients to a much greater degree than usual. The Montoya team is currently engaged in pouring over pathogen, immune data, gene expression and exercise data in an attempt to figure just what kind of chronic fatigue syndrome (ME/CFS) patient this drug works the best on. Suffice it to say that some results were achieved and others were not. It was a small study and these are the most difficult kinds of studies to get statistically significant results from.

    The Pharmaceutical drug companies were reportedly there in force with six people from Roche and others from three more drug companies. The Roche people and a group of chronic fatigue syndrome (ME/CFS) professionals meet for several hours Sunday night to decide what the next step will be. Based on who you talk to Roche is either enthusiastic or not about going following up with a larger study. (One problematic aspect of the present trial was its small size. By their very nature smaller sized studies increase the difficulty of getting a statistically ‘significant’ result. Much will undoubtedly depend on the results of Montoya’s analysis.

    The appearance of the Pharmaceutical companies underscores the potential impact of the Montoya study. This study was never about just about treating EBV/HHV-6 infected ME/CFS patients; it was about illustrating that a chronic infection of some sort plays a major role in ME/CFS. Montoya’s success would embolden efforts to the duplicate his results with other pathogens. Montoya is reportedly already looking into other pathogen subsets.

    The ‘Sith’ Returns: Novel Herpesvirus Protein Linked to Chronic Fatigue Syndrome (ME/CFS) and Depression
    K. Kondo. Identification of novel HHV-6 latent protein associated with mood disorders in CFS, depressive disorder, bipolar disorder and HHV-6 encephalopathy.

    This paper suggests that mood problems may be more a function of infection than behavior. Dr. Kondo identified a novel human herpesvirus-6 (HHV-6) protein that was present in Chronic Fatigue Syndrome (ME/CFS) patients with ‘psychological symptoms’ (whatever that means!) but not in healthy controls or ME/CFS patients without them. A serological study indicated that 71% of CFS patients with psychological symptoms and none of the health controls possessed the antibody against the SITH-1 protein (p<.0001).

    The Sith were a malevolent force in George Lucas’ Star Wars and the name is an apt one. Once Kondo realized the protein changed cellular calcium levels he checked for and found it in bipolar depression/major depression patients and but not in a host of other diseases including fibromyalgia or multiple sclerosis. Fifty-three percent of depression and 78% of bipolar depression patients possessed the antibody.

    Latent But Not Inactive. Intriguingly the SITH-1 protein is produced when HHV-6 is ‘latent’. Latency, it turns out, is a something of a misnomer; it simply means the virus is not replicating and eventually killing the cell and then spilling its virions by the millions into the bloodstream. Kondo’s study bears witness to the fact that viruses can be engaged in all sorts of damaging activities (such as generating damaging cytokines) that researchers have basically ignored. (A ‘latent’ central nervous system virus ,for instance, could prompt cells to produce immune agents called cytokines that are able to cause the kinds of symptoms found in ME/CFS).

    HHV-6’s persistence in the cell could conceivably have worse long term effects than if it actually killed the cell. The death of an infected cell sparks an enormous immune response and usually, if all goes well, a complete resolution of the problem. HHV-6’s mole-like behavior in its latent state could allow it to run well below the immune response and conceivably alter the behavior of cells for decades. What might a process like that look like? - perhaps a mysterious chronic disease?

    A Post-Infectious Mood Disorder Subset? Although Kondo’s study is very preliminary – the ground he’s opening – that a pathogen may be responsible for the mood disorders in some ME/CFS – is fascinating. Later in the conference Dr. White will note that the depression in ME/CFS is something of a puzzle and that they cannot predict in whom it will strike. Does this suggest some unknown biological factor – a latent central nervous system infection perhaps – could be a work? In another later talk Dr. Peterson will argue that ME/CFS patients with HHV-6 reactivation display neurological problems not seen in other patients.

    This study, too, is very preliminary and many questions remain to be answered. Dr. Kondo needs to more fully characterize the protein and his findings need to be replicated in U.S patients. (The HHV-6 Foundation is attempting to do that right now). Is mood disorder in ME/CFS synonymous with an HHV-6 infection of the nervous system? Is depression more prevalent in acute onset ME/CFS patients? Can Kondo’s study be replicated in US patients? Much remains to be done.

    A Foundation’s Focus. This kind of difficult to detect, smoldering’ infection is exactly what the HHV-6 Foundation is focused on. Dharam Ablashi, who co-discovered the HHV-6 virus in AIDS pateints while working as a virologist at the National Cancer Institute, warned that while the test probably won’t be available soon it could make a big difference when it does show up.

    "It may take years to get the assay validated and into commercial production, but will be worth the wait. This assay could identify large numbers of patients with CNS dysfunction who could benefit from antiviral treatment. The HHV-6 Foundation is working hard to help scientists like Dr. Kondo develop better assays”.

    All the more reason to contribute to the HHV-6 Foundation NOW.

    Ancient Retrovirus Alive and Kicking in Chronic Fatigue Syndrome (ME/CFS) Patients?
    B.T. Huber. EBV and IFN-a activation of the human endogenous retrovirus HERV-K18 and CFS

    The Symposium was full of interesting research but none was more eye-catching than Brigette Huber’s study. Dr Huber presented evidence suggesting that a reactivated ancient retrovirus embedded in our genome may be active in chronic fatigue syndrome (ME/CFS) (and multiple sclerosis (MS)) patients.

    About eight percent of our genome is comprised of broken up, degraded, useless bits of ancient retroviruses that many millennia ago somehow managed to claw their way in there and hang on for the ride. They’re almost all ‘dead’ but of these bits of defunct genetic material can ‘come alive’ the right circumstances and start producing proteins again. Most of them belong to the Human Endogenous Retrovirus K (HERV-K) family.

    Dr Huber’s study suggested that a small percentage of ME/CFS and MS patients may have a predilection for this zombie-like retroviral reactivation. She found that both MS and CFS patients (whose illness had been triggered by infectious mononucleosis) were at a higher relative risk for containing HERV-K18 variants known to induce superantigen activity.

    Why would she check for this in ME/CFS? Because some facets of the disease look very much like a ‘superantigen’ is at work in the disease. Superantigens are proteins that are able to induce an overly broad immune (T-cell) response that depletes the immune system over time. Not long after Dr. Huber’s presentation Dr. Klimas reported that the immune findings in CFS are indeed what you’d expect in a chronically over-activated immune system.

    HHV-6 – the Hidden Culprit? One intriguing scenario is the possibility that HERV-K18 activation could be the endpoint of an HHV-6 initiated viral cascade. HHV-6 is able to reactivate EBV and both HHV-6 and EBV trigger interferon production, all of which can trigger HERV-K18 activation. This means HHV-6 activity could turn on the HERV-K18 retrovirus in at least three ways; directly, by producing interferon, and by reactivating EBV.

    We see yet another potential CFS/MS connection here as well and why not? Seventy-five percent of MS patients meet the criteria for CFS and fatigue is the often their most disabling symptom. There are, of course, major differences between the two diseases, but they also share grey matter atrophy, impaired cerebral glucose metabolism, altered autonomic nervous system activity, HHV-6 reactivation and altered patterns of brain activity.

    This study is also quite preliminary. Most importantly Dr. Huber needs to actually show that HERV-K18 is indeed activated and contributing to the symptoms of ME/CFS. If it does we need to know which ME/CFS patients it is active in. Is it reactivated only in post-infectious mononucleosis (EBV) patients or is it also present in ME/CFS patients with HHV-6 reactivation. Dr. Huber’s subset, like Dr. Montoya’s may be fairly small.

    Luckily after some ‘startup funding’ to get her going by the CFIDS Association of America she’s received an NIH grant to study these issues. Congratulations to her and congratulations to the CFIDS Association for getting the project off the ground.

    A Smoldering Infection in the Heart? Chronic Fatigue Syndrome (ME/CFS) and Erythroviruses.
    D. Lassner. Erthroviral myocarditis and fatigue like symptoms

    Dr. Cheney has taken the field of cardiac dysfunction in ME/CFS and run with it. His idea (at least so far as I understand it) is that problems with energy production in heart cells, possibly related to ‘oxygen toxicity’, is impairing heart functioning – in particular – diastolic heart functioning in ME/CFS patients.

    So far as I could tell, Dr. Lassner, a German cardiologist, has no acquaintance at all with Dr. Cheney’s work. Nor are his studies focused on CFS patients but they do suggest some intriguing parallels. The kind of heart disease Dr. Lassner is focused on, myocarditis, is accompanied by some very CFS-like symptoms (fatigue, lassisitude, flu-like symptoms) and some somewhat CFS-like symptoms (shortness of breath, chest pain). He noted that the myocarditis patients lacked ‘drive’ and had to take frequent breaks. Their systolic functioning was normal but their diastolic functioning was impaired and they often difficult to diagnose. (Dr. Cheney was was reportedly interested in the presentation but did not ask any questions).

    It is Dr. Lassner’s contention that myocarditis – which is typically caused by a viral infection - is greatly under diagnosed and when it is diagnosed it’s frequently diagnosed incorrectly. Heart biopsies are the only way to tell which bug is present but they haven’t been done regularly in the US for 25 years. Dr. Lassner believes that uncovering what bug is present and treating it could save a substantial number of lives. Myocarditis, after all, is the leading non-accidental cause of sudden deaths in young adults.

    His extensive biopsy research in Germany indicates that Parvovirus B-19 and HHV-6 infection are the two leading causes of viral myocarditis there, followed by enterovirus and EBV. The prognosis with treatment (IVIG-parvovirus, interferon-enterovirus), however, is very similar to that reported by ME/CFS physicians; improvement often followed by relapse once one is off the drug followed by improvement once one goes back on it.

    Another Smoldering Infection? Could ME/CFS patients simply be undiagnosed myocarditis patients? It’s important to note that there are real differences between Dr. Lassner’s patients and the average chronic fatigue syndrome patient. When I asked Dr. Lassner if the myocarditis he saw could settle into a kind chronic non-progressive state (i.e. ME/CFS-like) he replied ‘No’ - without some sort of intervention the disease was slowly progressive. Furthermore X-rays should show inflammation in the heart – which has not been reported in ME/CFS.

    In his talk, though, he said it was possible for a virus to persist without killing the cells it had infected. This suggests that the same kind of ‘smoldering infection’ Dr. Kondo found in nerve cells could occur in heart cells as well and brings the question whether ME/CFS patients have some sort of infection that alters heart cell functioning without killing them. A similar process may be occurring with regard to HHV-6 infection and epilepsy.

    With regard to the diastolic dysfunction found most often found in ME/CFS patients. Dr. Lassner suggested that HHV-6 infection in the endothelial cells lining the blood vessels would be the most likely culprit. This is the type of infection, interestingly, Dr. Lassner felt was most likely to cause problems by altering cellular functioning rather killing cells. HHV-6 infected endothelial cells appear to secrete more pro-inflammatory cytokines which could result in constricted blood vessels, impaired capillary production and lead to reduced heart blood flows – all of which have been found in at least a subset of ME/CFS patients.

    Amazingly he reported that 16/30 genes in his list of genes with abnormal expression were identical to Dr. Kerr’s genes identified as abnormal. This is an almost unbelievable overlap. Since we didn’t have the actual data it was difficult to tell exactly where the overlap occurred e.g. was it in the Kerr’s short list of up/downregulated genes in ME/CFS or in a more general list of genes that may contribute to the disease. We'll have to wait for the paper.

    The work by Dr. Lassner’s group led by Dr. Uwe Kühl and findings from two other German cardiology centers (where biopsies are done routinely) have prompted the American Heart Association to alter it’s approach to heart biopsy’s and it recently outlined scenario’s which it believes warrant them. . Biopsies, then, are coming back – at least for a few carefully selected types of cardiac patients in the US. They are probably still not an option, though, for most ME/CFS patients – even those with cardiac abnormalities. (Dr. Lerner quickly stopped doing biopsies in ME/CFS patients after they experienced excessive bleeding.)

    Stress and Infection (= Chronic Fatigue Syndrome?) J. Kerr. Stress and parvovirus B-19 associated arthritis and chronic fatigue.
    It’s almost stressful how much ‘stress’ is popping around chronic fatigue syndrome (ME/CFS) research circles. Here Dr. Kerr examined people who’d come down with ME/CFS following a parvovirus infection. After looking at a range of factors, including stress, cytokines, cortisol, etc. he found that only a ‘stress index’ predicted which patients would come down with ME/CFS (and arthritis) after a parvovirus infection. An increased ‘stress index’ also was associated with increased levels of fatigue during the initial stages of the infection.

    There is something of a catch here. The patients were asked to assess their negative life events after they got ill. It’s possible, given the high levels of stress these patients were already under that they more negatively viewed their stress levels before they got ill than they would have if they were healthy. However, Dr. Kerr noted that his attention was drawn to this issue by the significant number of patients who’d indicated they’d lost relatives, were overworking, had been exercising too much, had been in a car accident, etc. and this is not the first time this finding has shown up.

    This finding suggests that poorly functioning stress response systems play a role in virally induced ME/CFS. Given the role the two stress response systems in the body; the HPA axis and sympathetic nervous system also play in modulating the immune response this is perhaps not so surprising. Dr. Kerr noted that stress has been shown to inhibit several aspects of the immune response including reduced NK cell activity and T-cell proliferation, reduced interferon Y levels and that it increases the likelihood of herpesvirus reactivation. It also increases the likelihood of one coming down with infection.
    He also noted that in 3 parvovirus ME/CFS patients with increased cytokine activity intravenous immunoglobulin IVIG therapy had been successful.

    Enteroviral Enigma No More?
    J. Chia. The role of enteroviruses in myalgic encephalomyelitis/chronic fatigue syndrome

    Besides his possibly groundbreaking work on chronic fatigue syndrome (ME/CFS) Dr. Chia turned out to wonderful guy as well. On that first lunch he headed right over to a table of patients and settled in. Hardly touching his food he readily answered everyone’s questions in detail. The day we weren't so lucky; the the head table already had a place set aside for him and they quickly snatched him. But who could blame them? His work is making many rethink their assumptions about pathogens in this field.

    Dig Deeper: For more on Dr. Chia's work click here and here

    He started out with a case report.

    Case Report #1 - A patient with an infection came to see him. Over time she recovered nicely but six months later she was back another different infection. This time she fell apart and after three months she was hospitalized. Gamma globulin (IVIG) injections helped. She improved and while after four months she still had fatigue, muscle pain, irritable bowel syndrome she was able to be active 3-4 hours a day.

    Two months later she relapsed severely. A stomach biopsy revealed she had an enteroviral infection. At lunch Dr. Chia says he sees this pattern again and again – a patient comes in with an infection and is apparently cured only to severely relapse (come down with ME/CFS) after another different infection. Something in that first infection appears to set these patients up for the knockout punch when the next infectious episode occurs. Dr. Chia is an infectious disease specialist so he’s in an excellent position to observe infectious onset cases of CFS.

    The Enteroviral Enigma. Dr. Chia’s goal here in this talk was to illustrate why some of the enteroviral studies of the past had failed. Enteroviruses have long been suspected in ME/CFS and the research started off with a bang with early studies showing increased levels of enteroviral DNA in a significant portion of ME/CFS patients. Attempts to replicate those studies had mixed results, though, and a once promising field of inquiry languished until Dr. Chia came on the scene.

    Dr. Chia has looked at this situation closely – too closely for a brain addled and increasingly writing challenged CFS patient such as myself to follow closely or even perhaps accurately. Hopefully this summary is more or less accurate.

    As late as 1995 a blinded, controlled study indicated that 41% of ME/CFS patient’s vs. 2% of controls had enterovirus RNA in their serum.

    Then if my understanding is correct something seemingly innocuous happened: one of the top researchers in the field (Robart) patented a new method to measure enteroviral RNA. The new test, which swept the field, created a new, and Dr. Chia believes, improper baseline.

    Essentially the test was unable to detect enteroviral RNA below a certain number of copies. Unfortunately many ME/CFS patients had lower RNA levels than the test could indicated but still much higher levels than healthy (or even as Dr. Chia will demonstrate) unhealthy controls.

    Trouble From the Top - In 1995 the leader of the NIH program, Stephen Strauss, reported in an editorial that he was unable to find any enterovirus in his patients. Strauss never published his results but his high profile as the leader of the NIH’s CFS effort put a substantial damper on the field. Dr. Chia believes Strauss’s results were correct but that he used the wrong test.

    When Dr. Chia used an updated version of the Robart (Chemicon) test to which a new primer had been added the enteroviruses were back; he found 38% of CFS patients vs. only 4% of the controls were positive. As disease severity increased so did the percentage of those infected – 70% of bedridden patients had it but only 12% of higher energy patients were positive.

    That result apparently convinced Dr. Chia to dig deeper and he began doing his stomach biopsies where he found much the same results; high percentages of positive patients (57%) and low percentages of positive controls (5%). Again the degree of infection seemed to match the severity of illness; only 25% of the ME/CFS patients with substantial infection were able to work but 54% of patients with lesser infection were.

    Short-term course of antivirals (interferon a/ interferon y) that resulted in significant improvements (but also generally a relapse following cessation of the drugs) suggested that the bugs were contributing significantly to the disease.

    Case Report #2. At this point Dr Chia showed a graph of a patient’s progress over a course of treatment. Her functional levels started off low and with the die-off prompted by IFN-y gamma treatment fell she got even less functional but eventually rebounded strongly and with the addition of Valtrex she was she able to return to full-time work. Several months after going off Valtrex she relapsed severely returning to lowest level of functioning Putting her back on Valtrex a second time helped but not to the extent it did before.

    Proving Viral Causality - It’s not easy to prove the infections found in ME/CFS cause or even contribute to the disease. Higher than normal pathogen loads suggest they might but do not prove that they do. The only really effective way to prove that X pathogen is responsible for all or part of Y disease is to identify the pathogen, hit it with the appropriate drugs, determine that its either declined or disappeared and then show improvement by measuring functionality, symptoms, aerobic respiration, immune status, etc. (all in the appropriate placebo controlled, double-blinded fashion).

    Unfortunately those kinds of trials are very expensive and very rare in ME/CFS. With regards to enteroviruses just identifying the pathogen can be problematic. When asked if he checked to see if the enterovirus had disappeared after his patients had gotten better on the anti-virals Dr. Chia said it had with the proviso even when the patients were ill it sometimes took several attempts to find it.

    (Chronic fatigue syndrome (ME/CFS) patients who have had upper endoscopies in the past can send biopsy samples to Chia for analysis. Kristen Loomis reported that the HHV-6 Foundation has been sending samples from ME/CFS patients to Dan Hartmann at Georgetown University Hospital, and has found enterovirus or HHV-6, in most of these samples. HHV-7, CMV and parvovirus B-19 have also been found.)

    Better Antivirals Needed. There is strong anecdotal (and some study) evidence that antivirals can dramatically assist a subset of patients but what the research world responds to rigorously delineated treatment trials. Those are much more difficult to do when you have less than stellar detection methods. Its rather remarkable that diagnostic difficulties plague many of the pathogens (HHV-6, enteroviruses, borrelia (Lyme) in question in ME/CFS. This is why the finding better tests is the chief goal of the HHV-6 Foundation.

    Another problem with the infections in ME/CFS is the general lack of efficacy of many of the antiviral drugs. They all help or even cure some patients but overall their performance is unsatisfactory. Some work fine only to have the patients relapse afterwards. Some patients that appear to be good targets for a drug do not respond while poor targets sometimes do.

    Dig Deeper: Antiviral Drugs in Chronic Fatigue Syndrome (ME/CFS)

    (One Montoya study found that, yes, ME/CFS patients with increased antibody titers did respond significantly better than those with low titers - a very important finding - but there where still those patients with high antibodies who had no response to the drug and patients with low titers who responded well; hence Dr. Montoya’s continuing attempts to find ‘Waldo’).

    There are also toxicity problems and most are expensive. Some require long duration treatments that patients cannot afford or are unwilling to try. Both Dr. Chia and Dr. Peterson vigorously asserted that more effective as well as less toxic antiviral drugs are greatly needed.

    Dig Deeper: See Part II of the Symposium Overview for future antiviral drugs

    Waiting on Technology - Indeed Dr. Chia wrote in his abstract that the “Development of antiviral drugs specific for enterovirus replication is of paramount importance”. In fact the definitive assessment of the enteroviruses role in ME/CFS awaits the creation of drugs able to fully knock it out. His abstract ends by stating that ‘controlled trials with future antiviral drugs will likely provide the ultimate evidence for the pathogenic role of EV in ME/CFS'.

    Once again, ME/CFS patients are waiting on the technology. This is all the more reason, of course, to ensure that organizations that are funding cutting edge research like the HHV-6 Foundation, the Whittemore-Peterson Institute, the CFIDS Association of American, MERUK and others are well funded. And even more reason to aggressively go after the golden egg of research funding – the National Institutes of Health - in the U.S.

    An interview with Dr. Chia is coming up shortly

    Thanks to the HHV-6 Foundation and PANDORA for their assistance in attending the Baltimore Conference, thanks to Tom Hennessey for getting me back and forth several times from DC (and as always thanks to my brother for his twisted but still much appreciated hospitality. Thanks to the HHV-6 Foundation for their comments on this paper).

    To The Symposium on Viruses in Chronic Fatigue Syndrome (ME/CFS): Part II

    The Symposium on Viruses in Chronic Fatigue Syndrome (ME/CFS) (June 2008): Part II
    by Cort Johnson

    A Neuro-Immune Fatigue Subset?

    D. Peterson. Antiviral treatment of patients with HHV-6, EBV and enterovirus: case reports

    There’s this 15-30% percent number floating around ME/CFS. Several doctors have spoken of the 20% of patients who seem immune to their approach. There’s about 20-25% dropout rate in behavioral studies. There’s the 25% ME group of really disabled patients.

    Then there’s Dr. Peterson 15-20% group. This is a group for whom the standard toolbox doesn’t fit; they don’t respond to supplements or the commonly used drugs and behavioral modification has no effect. Dr. Peterson thinks they have a different kind of disease altogether. He calls them the neuro-immune fatigue group.

    These patients generally have headaches, cognitive problems, paresthesias (pins and needles feelings), autonomic dysfunction (presumably increased heart rate, trouble standing, etc.), abnormal MRI reading and SPECT scans. Cerebral spinal fluid (CSF) studies indicate increased total protein, myelin basic protein, lactic acid, lymphocytes and opening pressure.

    They have active viral infections usually with cytomegaloviruses, HHV-6, Epstein-Barr virus (EBV), a gamma herpes virus and enteroviruses. Their gene expression, cytokine and protein expression results suggest their immune systems are chronically activated – as one would expect.

    The antiviral drugs Dr. Peterson uses to treat these patients include Foscavir, Valcyte, Cytovene, Zovirax, Valtrex, Vistide and Ampligen (approved for use in Canada).

    A Cancer Subset? Dr. Peterson reported that a subset of his patients with chronic HHV-6 infection exhibit a kind of process – called T-cell receptor gene re-arrangement – that’s usually found only in lymphoma patients. This process apparently increases the risk of T-cell becoming cancerous. The Whittemore-Peterson Institute is reportedly focusing on this subset of patients.

    Dr. Peterson’s work, if substantiated, underscores how important subsets may be in this disease and how incredibly damaging researchers inability to ferret them out has been. A twenty percent subset in a disease will do two things; it will make it difficult to find consistent findings for the other 80% of the patients and make it almost impossible to detect the subset itself If Dr. Peterson’s subset is a truly different kind of patient the 20% subset represents an ongoing tragedy. (One study of the longterm effects of ME/CFS did not find increased mortality in the disease).

    Dr. Peterson’s work, too – despite his years of experience - must be also regarded as ‘preliminary’ as is any unpublished work. In order to truly impact the course of ME/CFS research must be published and replicated – hopefully by different researchers. The word is, though, that Dr. Peterson, a busy physician will, with the help of Judy Mikovitz, the new Director of Research at the Whittemore-Peterson Institute (WPI) will be publishing shortly.

    Dig Deeper: The Whittemore-Peterson Institute

    Antiviral Drugs – Hope on the Horizon?

    Prichard, New Developments in therapies for HHV-6 Infection

    ‘Precious few molecules with good activity against HHV-6 have been identified and none have been approved.” M. Prichard

    Dr. Prichard noted we have a long way to find a really good drug against HHV-6. One problem with the current batch is dose-related toxicity. At high enough doses they can indeed kill the bugs but at the risk of injuring or killing the patient. Dr. Prichards presentation suggested that the next round of antiviral drugs will be more effective and less toxic.

    In Development

    Artesunate - Artesunate is a well tolerated drug approved for malaria (in Europe) that possess antiviral activity as well. In vitro (lab) studies found it was highly effective against one of HHV-6’s cousins; the cytomegalovirus.

    An HHV-6 Foundation funded study indicates artesunate also effectively inhibits HHV-6A in the lab. This drug is particularly promising because, in contrast to ganciclovir and foscarnet, it hits HHV-6 early in its life cycle. If HHV-6 produces a kind of smoldering infection that alters cell functioning in ME/CFS and other diseases then hitting it early will be critical. What a boost it would be to find an already approved drug that was effective against HHV-6.

    Cycloprovir – analogue of ganciclovir but potentially much more effective against HHV-6. (Valcyte converts to ganciclovir in the body. Ganciclovir interferes with viral replication.

    CMX001 – a variant of Cidofovir – is highly effective again many DNA viruses and is 3x’s better than Cidofovir against all herpes viruses in the lab. Its antiviral activity in animal models is very good as well. In the first clinical study it was well tolerated.

    CMV423 – a new compound very effective against HHV-6 and cytomegalovirus

    HPMP-5-azal – Six times more effective against HHV-6 than Cidofocir. Much more efficient and much less of the drug is needed. This is important because toxicity is a big problem with cfidovir. Possibly a big hit.

    Marabavir (MBV) – inhibits cytomegalovirus replication. Currently in Phase III trials. Good against EBV. Contrary to previous reports, possibly good against HHV-6. About 50-100 times more efficient than cidofovir in some tests.

    Arysulfone derivatives – good antiviral activity, among most potent of anti-virals.

    Valomaciclovir and foscarnet-AZT and HHV-6. K. Yao.

    Laboratory studies suggest that using Valomaciclovir and foscarnet-ZT in combination resulted in greater than 90% suppression of HHV-6 after three days. This drug is also being tested in a clinical trial at the University of Minneappolis to treat EBV mononucleosis.

    Report From the Bench: An ME/CFS Physician on Antiviral Treatments in Chronic Fatigue Syndrome (ME/CFS)

    K. De Meirleir Antiviral Treatment Strategies in Chronic Fatigue Syndrome
    "Today using combinations of immunomodulators, antivirals, nutriceuticals and antibiotics we are able to obtain an acceptable clinical results in 70% of CFS patients.”

    Dr. De Meirleir has treated 1000’s of ME/CFS patents. He pointed out how little hard data there was on the efficacy of anti-viral treatments in the disease.

    Antiviral Treatments

    Immunoglobulins – could benefit ME/CFS patients by neutralizing viral antigens and by rebalancing the immune system. They’ve had mixed results in placebo-controlled studies. One study on adolescents suggested they can be very effective. He used low doses of IgG1 or IgG3.

    Antivirals – Again we hear the big problem with using antivirals is diagnosis. Physicians need solid and reliable viral markers to determine which patients antivirals will be effective with. Until they can get them they’ll continue to use broad spectrum antivirals and immuno-modulators that may or may not be effective against a particular pathogen.

    Ampligen – physicians using the drug now have 20 years of experience with it. He noted that two double-blinded, placebo-controlled and two open label studies have found increased cognitive functioning and exercise capacity. Ampligen may be particularly effective in post-EBV cases of ME/CFS.

    Kutapressin (Nexavir) – in test tubes Kutapressin (now called Nexavir) inhibits EBV replication and blocks EBV from infecting macrophages. Anecdotal activity suggests that Kutapressin works. Dr. Enlander has unpublished data indicating that 63% of ME/CFS patients ‘respond’ to a brand of Kutapressin he uses called Hepapressin + B-12. Dr. De Meirleir found that 70% of his patients responded quite well to Nexavir (20+ increase in Karnofsky scale in 6 months. This is about double the increase Dr. Cheney’s patients showed on porcine cell factors).

    Aciclovir – no beneficial effects found over placebo. No positive immunological effects.

    Amantadine – inhibits viral infection of the cell and increases dopaminergic activity in the brain. Amantadine has been used to relieve fatigue in MS patients for years. Dr. De Meirleir said it does relieve fatigue in CFS patients as well but a cross-over study found no significant benefit and increased numbers of side effects.

    Thymalfasin (Zadaxin) – new drug used in Italy and Asia to fight chronic hepatitis C. Excellent results reported in off-label uses on chronic fatigue syndrome (ME/CFS) patients in Europe. A placebo-controlled trial is planned.

    Azithromycin – an antibiotic that appears to have antiviral properties and is able to penetrate the blood-brain barrier, an important consideration with central nervous system infections. One study reported 50% response rate in ME/CFS. His and Dr. Nicholson’s findings in the US are similar.

    The Future - is about using new tools such as gene and protein expression and better viral diagnosis protocols to put ME/CFS patients in the correct subset and then targeting the right (new) antivirals and other therapies at them.

    (This might not be as difficult as it sounds. If gene and protein expression technologies can just find these subsets then the rest, at least so far as I understand, might be fairly cheap and easy. From what I’ve heard it’s not expensive or particularly difficult to test for a single or couple of upregulated genes – the key is finding them. )

    (The gene expression news right now is ‘pretty good’. Dr. Kerr was able to replicate his former results – a big step forward – and it seems like almost every major group - from the CDC to the Whittemore-Peterson Institute to the Montoya studies to the NIH – is taking a hard look at them. Dr. Kerr believes he has found some subsets but it’s not clear yet how ‘tight’ they are.

    (Gene expression studies are not at the point, though, where they can identify, say, a central nervous system HHV-6 subset. Dr. Kerr’s repeated identification of high levels of activity in a gene known to be upregulated during Epstein-Barr Virus infection suggests he could be beginning to open up a viral reactivation subset. The Dubbo gene expression studies, on the other hand, found few meaningful correlations in their gene expression studies of their acute onset post- infectious chronic fatigue syndrome (ME/CFS) and Dr. Lloyd does not believe they will play a major role.)

    (One key to improving gene expression’s efficacy may be doing complex analyses that combine clinical, laboratory and gene expression data together to ferret out specific sets of patients. This was tried in 2006 in the Pharmocogenomics projects to quite mixed results. The winner of the CAMDA competition that used the same dataset did, however, use complex multidimensional analyses to pick out a gene (FORKHEAD BOX gene) that was associated with immune depletion. Perhaps in the absence of reliable pathogen data these complex multi-variate analyses will eventually be able to pick out pathogen (and other) subsets.

    (The FORKHEAD BOX study was one of the most tantalizing studies to come out of the Pharmocogenomic’s study effort. One wonders if, with the financial hit the CDC’s CFS research program has taken funding wise, if it was just left on the shelf.)

    (If researchers can find key indicators across a variety of tests they should be able to formulate an algorhythm that could be cheaply tested for. Such an algorhythm could be something like ‘Subset A” = low cortisol plus X, Y, Z upregulated genes plus D and C parameters. These studies are expensive and will require a boost in federal funding for them to come to fruition. )

    Dubbo: Not Dead At All
    Andrew Lloyd. Investigation of the pathogenesis of post-infective fatigue in the Dubbo infection outcomes study (DIOS)

    Dubbo (pronounced ‘duh-bow’ not ‘dew-bow’) has had its troubles lately. When funding for the CDC’s CFS research team tanked they were cast adrift. Attempts to get several NIH Neuroimmune CFS Grants inexplicably failed leaving them in even deeper waters. One wondered if the Dubbo’s projects time – once one of the shining lights of ME/CFS research – was over. Somehow, though, they’ve managed to keep going.

    The Dubbo study’s finding haven’t exactly lit the ME/CFS world on fire either. Dr Lloyd’s rather categorical announcement that neither infectious activity nor immune over activation was driving this illness didn’t endear him to a good number of researchers. It didn’t help that the Dubbo studies have found more about what chronic fatigue syndrome is not than what is; thus far their results have suggested ME/CFS is not due to an inability to fight off the infection or an over-active or under-active immune response.

    Dr. Lloyd’s recent statement that based on his findings he believes the jury is still out as to whether gene expression will tell us anything about this disease was probably not eagerly greeted in many quarters. One began to wonder if the Dubbo study was ever going to announce anything positive at all about this disease.

    Dig Deeper: the Dubbo studies in review

    A Remarkable Unanimity. But the Dubbo studies are back and in a big way. The data from all the pathogen cohorts (EBV, Ross-River and Q-fever) have now been analyzed and they all show a remarkable unanimity. In each of the cohorts the acute symptoms (fever, sore throat, etc.) fade leaving behind a fatigue, muscle and joint pains and, in some, mood disorders.

    The rate of post-infectious fatigue or ME/CFS is almost identical at 12 months (6%) and 24 months (3%) among the three cohorts. The key findings of the early studies were repeated in each of the other pathogen cohorts. It turned out the prior findings weren’t a case of concentrating on the wrong pathogen (EBV) as some have suggested; these appear to be standard outcomes for acute onset ME/CFS patients.

    Different Pathogens / Different Patients = Same Disease: Consider how different these pathogens are to get a sense of how remarkable these findings are; the Epstein-Barr Virus strikes younger people, the Ross River Virus hits middle-aged people and Coxiella burnetii stricks only middle-aged males in the farm community. Two are viruses and one is a bacteria and they all produce different symptoms in the beginning but all produce not only the same kind of ME/CFS but they produce the same rates of ME/CFS a remarkable finding!

    Until the latest study (see below) the only abnormality the ubbo groups been able to distinguish was that the patients who stayed ill got whacked hard early in their illness. Dr. Vollmer-Conna explained that the initial illness severity was not a trivial factor; it was in fact a surprisingly strong indicator of who was going to stay ill. It also appeared to predict duration as well; the people who got really sick early on generally stayed sicker longer.

    Still this wasn’t much – it was after all just a self-reported symptom – not exactly the kind of fact that could turn the scientific world on its head. It did suggest, though, that the problem in chronic fatigue syndrome (ME/CFS) occurred very early - during that period when the patients had little idea they were fighting off anything more than another cold and certainly long before they could begin to guess their lives were being perhaps irrevocably altered. The next phase of Dubbo studies may have uncovered a piece of what happened.

    Breakthrough in Dubbo?

    Uté Vollmer-Conna. Cytokines in post-infective fatigue.

    Dr. Vollmer-Conna started off her talk by noting how disappointing the cytokine findings thus far had been. Cytokines – immune agents that travel through the blood turning on immune cells when the body is fighting off infection – produce the ‘sickness response’ that makes us so miserable when we are ill. The infectious onset and similar symptoms seen in ME/CFS seemed to make cytokines the perfect fit for this disease but thus far the Dubbo studies had found no evidence that cytokine levels were increased as the disease progressed.

    Armed with evidence suggesting the early stages of the disease were the most important they took a close look at the early cytokine data. They found that the people with the severest symptoms (i.e. the soon to be ME/CFS patients) had the highest levels of cytokines, but perplexingly this was only true in the acute illness and not later in the ME/CFS phase.

    An Illness Begins Unraveling? This suggested that the chronic fatigue syndrome (ME/CFS) patients had a tendency to pump out more cytokines than normal early during an acute infection. Next they asked why. They found the ME/CFS patients had very significantly increased risks of carrying two variants of genes that could increase their symptoms during illness. (Different types of a single gene (a polymorphism) are common in population. Typically these variants tend to code for stronger or weaker gene activity).

    One of these gene variants coded for increased pro-inflammatory cytokine activity; the other for decreased anti-inflammatory activity. Having either by itself significantly increased the risk of illness but the risks were increased considerably more in people who carried both of them – these were pretty strong indicators.

    Their findings suggested that people who carried these gene versions strongly tended to (a) get sicker early in the infection, (b) produce more cytokines early in the infection and (c) come down with ME/CFS. In short the genetic predisposition of these patients seemed to set them up for a particularly strong pro-inflammatory immune response early in an infection.

    The Next Step. But then what? What might high cytokine levels do? I asked Dr. Lloyd, Dr. Vollmer-Conna and Dr. White about this. The Dubbo’s team current theory is that high cytokine levels early in the infection alters patterns of brain functioning. Specifically they believe they thrust the brain into a state of hyper-vigilance in which it over-reacts to signals coming from the body. They suggested ME/CFS was a kind of post-traumatic stress disorder with the proviso that the brain was overreacting to internal, physiological signals (as opposed to cues in the outside environment.)

    This theory, which is close to the interoceptive theory, suggests that the state of illness disappeared from the body but not from the brain. The brain - believing the body is still sick – continues to produce sickness signals; it is these unrelenting signals that damage the HPA axis, immune system, and the other systems involved in chronic fatigue syndrome (ME/CFS) etc. over time.

    Dr. White noted that these signals all occur under the level of consciousness – in the subconciousness. Given the benefits I’ve accrued from the Gupta Amygdala Retraining program which attempts to combat negative subconscious activities I asked them what they thought about it. I noted that meditation and other techniques (which the Gupta program among others employs) have been shown to reset autonomic nervous system functioning (i.e. retrain the brain). Dr. White felt that the program was good but that the problem may not specifically originate in the amygdala.

    Dig Deeper: The Amygdala Retraining Program - A blog plus patient reports

    The location of the problem, if indeed there is one, is a matter of some dispute. Ashok Gupta believes it originates in the amygdala, Dr. White in the anterior insular, Dr. Baraniuk in the Papez Circuit, Dr. Lloyd in another region, Dr. Chaudhuri and apparently Dr. Reeves in the basal ganglia. Most of these are in similar parts of the brain that effect cognition, emotions and autonomic nervous system functioning. A good deal of brain imaging research is going on right now and we should know fairly soon if these researchers are on the right trail

    Questions/Questions – Given the Dubbo studies inability to find overt immune dysfunction/pathogen activity in a post-infectious set of ME/CFS patients does this mean that the immune/infection question has been answered? Apparently not to everyone’s satisfaction.

    The CDC is taking another look at the Dubbo team’s long term cytokine data and the HHV-6 Foundation questions whether the right cytokines were measured. The Foundation believes it’s possible that original infections reactivated a central nervous system pathogen (HHV-6, enterovirus, endogenous retrovirus). They also question whether they were cleared out. Specifically they question whether the tests used to assess EBV activity would adequate to detect an active infection. They suggest that EBV EA antibody tests should have been used.

    (The pathogen diagnosis questions really bedevil this field. During the lunches several researchers noted now difficult it was to find evidence of X pathogen in blood when biopsies (or autopsies) revealed it was readily present in an organ. Throw in the possibility of a central nervous system infection and at least some researchers raise serious questions arise about the efficacy of blood-based tests. A recent study showed that HHV-6 can persist in the spinal fluid long after it’s disappeared from the blood. Another study found no evidence of HHV-6 infection in the spinal fluid even though later autopsies suggested it had been active in the brain )

    (Dr. Klimas asked if the team had looked to see if virus’s such as HHV-6 had reactivated as the patients got ill. Could the initial pathogen have cleared out a space for another virus to pop up? Dr. Lloyd didn’t know and felt the jury was still out on that question. )

    Biomarker (!)(?)

    Nancy Klimas, Immune Markers in Viral Reactivation

    Dr. Klimas looks at ME/CFS from the eyes of an immunologist and what she sees is an immune system that’s been revved up too long and has begun to bug out. Simply put ME/CFS patients immune systems are like auto’s with 250,000 miles on them and are fraying at the seams.

    What in the body is putting chronic fatigue syndrome (ME/CFS) patient’s immune systems through their paces? Dr. Klimas believes a chronic viral infection is the culprit but in something of a departure from others believes it is found not in 15-20% of patients but in a ‘large subgroup’ of them.

    The evidence for immune activation is long and includes increased levels of cell suicide, poor NK and T-cell functioning, increased pro-inflammatory cytokine production and macrophage abnormalities.

    NK cell dysfunction is a key immune problem in ME/CFS but it has a catch – a big catch – it’s expensive to test for. This has lead Dr. Fletcher and Dr. Klimas to look for a cheaper test that reflected poor NK cell functioning and they think they’ve found one – neuropeptide Y. In doing so they got an added bonus: the cheaper test may provide a clue to what’s causing the problem.

    “A Very Good Biomarker for ME/CFS”

    We regularly hear that this or that may be a biomarker for ME/CFS but the years drag on there’s still no biomarker. Now Dr. Klimas says CD26 - a receptor found on immune cells and in soluble form in the blood – is ‘a very good biomarker for this disease’. This receptor apparently reflects immune depletion and is significantly, very significantly decreased (p<.0000) in ME/CFS patients.

    Establishing A Neuro-immune Connection – Neuropeptide Y - The biomarker is big but there was also big news regarding a substance called Neuropeptide Y (NPY). We hear a lot about a neuro-immune connection in ME/CFS but little direct evidence of it. Neuropeptide Y may provide the bridge between the two that researchers are looking for.

    NPY is stored in the nerve terminals of the sympathetic nervous system (SNS) and is released in conjunction with SNS nerve agents called catecholamines (norepinephrine, epinephrine). Recent evidence suggests that the activity of the SNS – which is part of the stress response - is increased in ME/CFS. Given that it stands to reason that NPY levels would be increased in ME/CFS as well - and they are – quite significantly so (p<.001). Intriguingly given the stress connection NPY levels are associated with an increased stress index and, given that, not surprisingly with increased anger, confusion, frustration, etc.

    Dig Deeper: Nancy Klimas on immune dysfunction and the future in chronic fatigue syndrome (ME/CFS)

    The Fletcher/Klimas team is one of the few that’s been able to crack the NIH. They’ve been getting NIH grants to study ME/CFS patients for over 15 years now. I asked Dr Fletcher if getting a grant was any easier now. She looked at me and laughed and said ‘Are you kidding?’. Their latest grant – which examines immune measures when ME/CFS patients are experiencing ‘good days’ and ‘bad days’ - took three rounds to get approved. She said it was roundly rejected until it was finally approved and that the makeup of the committee was key.

    Dirt in the Gears
    Suzanne Vernon - Genetic variation and altered immune activity in Chronic Fatigue Syndrome

    Dr. Vernon’s talk really got some people buzzing. She’s been searching for patterns in large, complex data sets that contain gene expression, gene polymorphism and laboratory data. This is the kind of unique cutting edge stuff that exemplified the Pharmacogenomics efforts. This is not cutting edge ME/CFS stuff its cutting edge period. It’s a new way of looking at complex multi-systemic diseases.

    Her evidence suggests ME/CFS really is a multi-systemic disease but on a scale that hasn’t been comtemplated before. We’re going to wait for the papers publication- hopefully in a few weeks – but suffice it to say that her recent evidence suggests that entire systems – not just x or y types of cells – but entire systems are operating abnormally in ME/CFS. It’s a fascinating thesis.

    The HPA axis – a important part of stress response system - appears to be ground zero in this scenario of systemic derangement. Dr. Vernon was the leader the CDC’s Pharmacogenomic’s projects which ended up again and again pointing at the HPA axis, in particular, at the adrenal stress hormone cortisol. Since then the CDC has run off a nice string of ‘successful’ papers on the subject. In the abstract for her talk Dr. Vernon put the HPA axis front and center stating that “hypoactivity (reduced activity) of the HPA axis leads to neuroendocrine and immune alterations”.

    What’s the evidence for that? And what kinds of alterations is she talking about? We’ll have to wait for the paper.

    Dig Deeper: the Pharmacogenomics Papers - the Overviews

    The Fatigue Syndromes

    An Overview of Post-Viral Fatigue: CFS or What? By Peter White

    As time goes on researchers are trying to dig deeper and deeper into the ‘fatigue syndromes’. Dr. White a well known UK psychiatrist asked whether the post-viral fatigue commonly after infectious mononucleosis (glandular fever) is different from chronic fatigue syndrome (ME/CFS).

    The fatigue after infectious mononucleosis is not trivial; studies show that about 40% of IM patients will complain of fatigue six months after the onset and that 12% will go so far as to see the doctor for it within a year. Most do appear to recover over time.

    Mood disorder, PVFS and ME/CFS - Most people who get post infectious fatigue syndrome (PIFS) do not come down with CFS. They often suffer from depression early on but it disappears quickly. Interestingly Dr. White stated the depression process found in ME/CFS is kind of unique; they could find all sorts of factors that could predict who will get depressed in PIFS but they couldn’t find them in ME/CFS. Indeed Dr. White was clear that ME/CFS is not – as was proposed for years – a kind of atypical depression.

    Dr. Enlander asked about the relationship between mood disorder and ME/CFS. Dr. White felt it was quite complicated. Depression is a risk factor for chronic fatigue syndrome but it is not a ‘big driver’ for it; i.e. other still unelucidated factors than depression are much more important in producing the disease. He noted that many ME/CFS patients are not depressed.

    PVFS and ME/CFS: similar but different - That both PVFS and ME/CFS patients were more likely to have seen their doctor for fatigue before they became ill suggested that some processes that later became amplified were already present. A finding that PVFS patients tended to experience more infections than normal before they come down with PVFS suggested they may have had immune problems beforehand. (Dr. Chia will report he sees the same process). CFS patients, on the other hand, tended to have more mood disorders than PVFS patients or healthy controls before they became ill. PIFS patients also tended to suffer from insomnia while CFS patients tend to experience hypersomnia (increased sleep).

    Interestingly data is emerging to suggest that not all infections trigger chronic fatigue syndrome. Flu pathogens, for instance, do not appear to. ‘Just for fun’ Dr. White guessed that about 20,000 people in the US come down with chronic fatigue syndrome (ME/CFS) after having infectious mononucleosis every year (60/day).

    Activity and ME/CFS - Dr. Bell asked what role activity level prior to getting sick played in the disease. Dr. White replied that evidence is emerging that both decreased and increased activity levels put one at increased risk of ME/CFS. He noted that people who experienced fatigue and kept exercising had an increased risk of coming down with ME/CFS.

    Dr. Lloyd noted that behavioral therapies were very helpful early in the illness. This was an interesting statement given evidence that people who try to bull their way through it (or exercise) place themselves at increased risk. Apparently the behavioral paradigm for ME/CFS no longer includes ignoring or denying the manifestations of the illness (???).

    One wonders if these behavioral therapies are actually reducing activity levels? Or if their new focus on ensuring one gets enough sleep, for instance, is particularly early in the disease? In an upcoming interview Dr. Friedman will point out that most ME/CFS patients are too active for their own good.

    Thanks to the HHV-6 Foundation and PANDORA for their assistance in attending the Baltimore Conference, thanks to Tom Hennessey for getting me back and forth several times from DC and thanks to my brother for his twisted but still much appreciated hospitality. Thanks to the HHV-6 Foundation for their comments on this paper.

    To The Symposium on Viruses in Chronic Fatigue Syndrome (ME/CFS): Part I

    [This Message was Edited on 08/12/2008]
  2. karinaxx

    karinaxx New Member

  3. karinaxx

    karinaxx New Member

    Its nice to see a old name here; there are so many new ones.
    Yes , you are correct, i was in Bali and everything else you named.
    I am back in India, for now.

    It is a long story how i got better and i think there were several factors involved which helped in that.But i also have to add, i am far from healed and i have not found the magic cure.

    I promise i will come up with a update on my improvment in the next few days.
    I know i promised, i was just so busy with life and a lot of problems still in need to be solved.
    I also wanted to be sure that it sticks and i am not getting worse again.
    But as far as i can say now, i am still getting better, compared with before, where i did the opposit.

    About the Neuropeptide Y i know absolutly nothing and it would be nice if you could enlighten me about it.

    warm wishes

  4. SpecialK82

    SpecialK82 New Member

    so much for posting this! I find all this research intriguing and am working on deciphering it through the brain fog.

  5. jasminetee

    jasminetee Member

    Good to see you back here. :) Thanks for posting this, it helps us see more about Montoya's study which many of us are wondering about. I find it interesting that some PWCs with low viral titers responded well to Valcyte while other PWCs with high titers were non-responders. I don't know if you know, but I was on Valcyte for 7 months last year but I was a non-responder.

    When I read this in the article I knew it described me:

    I'm in the "neuro-immune fatigue group.

    These patients generally have headaches, cognitive problems, paresthesias (pins and needles feelings), autonomic dysfunction (presumably increased heart rate, trouble standing, etc.), abnormal MRI reading and SPECT scans. Cerebral spinal fluid (CSF) studies indicate increased total protein, myelin basic protein, lactic acid, lymphocytes and opening pressure.

    They have active viral infections usually with cytomegaloviruses, HHV-6, Epstein-Barr virus (EBV), a gamma herpes virus and enteroviruses. Their gene expression, cytokine and protein expression results suggest their immune systems are chronically activated – as one would expect."

    I got CFS after coming down with EBV.

  6. Rafiki

    Rafiki New Member

    Enormously interesting.

  7. karinaxx

    karinaxx New Member

    nice to see your still here. i did check in from time to time and was reading through the post, especially the ones who reported on the valcyte trials.
    Thank you so much for beeing one of the pioneers and trying for all of us.
    It was dissapointing that the trial did not seem to get as much improvement for everyone as we ALL had hoped for!

    I am sure it must have been so frustrating for you!
    Are you in any way worse now?

    To all the others,
    your welcome and Cort Johnson is having a website you can suscribe for the news letter and get all his reports.(google phoenix, cort johnson)

    take care everyone

  8. jasminetee

    jasminetee Member

    Thanks so much for your kind thoughts. I'm worse actually but I'd been declining for 6 years before trying Valcyte so I don't know if my present condition is attributable to Valcyte or not.

    I was very depressed when I found out I was a non-responder after being on it for 7 months. Now I'm wondering if it was all the fruit juice I drank every day that interfered with absorption. There's new evidence about juice affecting meds that just came out.

    I suppose I can always repeat taking it in the future if they find out more about this.

  9. cfsgeorge

    cfsgeorge New Member

    This is really great info! Thank you for posting it! It's really getting to the root cause of CFS.

    I am in southern california and i was referred to dr. john chia, an infectious disease specialist who only treats CFS. Unfortunately, he has a +4month waiting list. In addition, my PCP says all his CFS referalls to him have not seen any improvement. I'm sure dr chia is a wonderful man and that every dr is doing their best in treating CFS. However, i feel that so little is known about the root cause of CFS that most "aggressive" or specific CFS treatments(anti-virals) will fail at the cost of more pain and dissapointment to the patient. It's like treating all the symptoms and opportunistic infections of AIDs w/o knowing or targeting the HIV.
  10. ladybugmandy

    ladybugmandy Member

    hello tee.. i didnt respond to valcyte alone (i tried it for a long time) but am responding to valtrex + valcyte.

    dr. ablashi recently told me that valtrex is much better for EBV.

    i am wondering if you have ever tried valtrex.

    thank you

  11. Jayna

    Jayna New Member

    so I can refer back to it later on.

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