tag:blogger.com,1999:blog-34469117676117712822024-03-08T06:38:37.412-08:00HOPE FOR FM AND CFIDS SUFFERERSFibromyalgia Researchhttp://www.blogger.com/profile/13598167140223702345noreply@blogger.comBlogger56125tag:blogger.com,1999:blog-3446911767611771282.post-25283269194677521822011-02-27T00:36:00.000-08:002011-02-27T00:36:28.573-08:00Is XMRV Research Dying?The recent weeks have left one to wonder - is XMRV becoming a dead issue like all other previous "causes" of Chronic Fatigue Syndrome? On the other hand, the neuropsychiatric psychobabble has begun to drown out good science.Fibromyalgia Researchhttp://www.blogger.com/profile/13598167140223702345noreply@blogger.com13tag:blogger.com,1999:blog-3446911767611771282.post-16877219186991550602011-02-19T20:12:00.000-08:002011-02-19T20:12:48.659-08:00Watershed Paper Provides Conclusive Evidence of Underlying Pathology of ME/CFS and FibromyalgiaThe study "Adrenergic and Sensory Receptor Expression on Leukocytes Increases After Moderate Exercise in Chornic Fatigue and Fibromyalgia" by Alan Light et. al clearly demonstrate the physiological processes behind Chronic Fatigue Syndrome. Like many of the good papers that have come out, Dr. Light found himself having difficulty getting it published. <br />
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In simplified terms, you've got the muscles, a messenger in between, and then the recipient (nerve endings). The situation that results in Fibromyalgia and ME/CFS is as follows: Following muscle injury, white blood cells pick up certain chemical signals from the muscles, and pass them on to the nervous system, specifically the sympathetic nervous system. Using currency as an example: Excercise A produces 5 units of fatigue, and white blood cells in the muscles read 5 units of fatigue, and is supposed to pass on 5 units of fatigue to the central nervous system, but instead passes on 50 units of fatigue to the nervous system, or alternatively the white blood cells misread the signal, and pass on 50 units of fatigue to the nervous system. So in essence, the sympathetic nervous system is receiving a forged document.<br />
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How does the mechanism fit in? In both CFS/ME and Fibromyalgia, acid-sensing ion channels, P2X4 and P2X5 purinergenic receptors, adrenergenic receptors, transient vanilloid type receptors and IL-10 were upregulated. The only difference was that in Fibromyalgia, P2X4 (Pain signals) and TRPV1 (receptor responsible for binding capsaicin - causing burning pain) was dominant, while in CFS P2X5 (Fatigue signals) was dominant. The effects were that changes occurred within 30 minutes of exercise in both disease cohorts, while in normal subjects, there was a considerable delayed onset, returning to baseline within 48 hrs. The amounts measured in endurance athletes after running a marathon did not even come close to the levels attained in disease cohorts. Incidentally, activation of P2X4 receptors has the effect of lowering blood volume, and increasing vascular resistance. <br />
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The effect is that the brain perceives the body to be under tremendous stress - it is well established that stress fundamentally disrupts the HPA axis (There is nothing better than pain for disrupting the HPA Axis!). The brain then sends signals for bodily functions to slow down - which involves downregulating mitochondrial function. It also means an increase in serum cortisol early on, followed by a period of adrenal fatigue. Essentially, earlier studies on pain amplification in Fibromyalgia shed some light, but we now have a mechanism. It was earlier thought to be as the result of too much substance P at the nervous system level. It is mechanism that has been around since the mankind: when it hurts or when fatigued, the body sends a signal to the rest of the body to slow down.<br />
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How does this fit in with XMRV? Much research needs to be done on this. XMRV enters the cell via XPR1, which is a G-protein coupled receptor, which in turn invokes a reaction cascade in the cell. Retroviruses rely on retroviral promoters to replicate once they are integrated in human DNA. XMRV could act by enhancing the transcription of receptors involved in pain signals if the sequence of the XMRV promoter also binds to the same region that codes for pain receptors on the human genome - alternatively, XMRV triggers a signalling cascade through a G-Protein coupled receptor that upregulates pain receptors. The effect can be further enhanced by cytokines triggered by XMRV.<br />
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These findings create optimism in finding small molecule therapeutics for both disorders, however it does not address the underlying viral pathology. The ideal drug design target would be inhibitors of P2XR4 and P2XR5 - however the risk of side effects is always there with small molecule therapeutics. One of the therapeutics Lyrica (Pregabalin), works by blocking pain transduction by Gabaergic mechanisms. However, it is a dirty drug, targeting other systems as well.Fibromyalgia Researchhttp://www.blogger.com/profile/13598167140223702345noreply@blogger.com15tag:blogger.com,1999:blog-3446911767611771282.post-56139762074451778952011-02-19T16:42:00.000-08:002011-02-19T16:42:13.386-08:00New Monkey StudyOn one of my previous posts, I mentioned that a protein called APOBEC3 strongly exhibits retroviral replication. A recent study by Robert Silverman of the Cleveland Clinic confirms this finding. Five macaque monkeys were infected with XMRV - they showed an initial viremia, subsequently the virus became very difficult to find in the blood, but when the monkeys were sacrificed, the virus could easily be found in the spleen, lungs, lymphoid tissues, and prostate.<br />
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Ironically, the same patterns in certain blood cells were noted that exists in a cohort of ME/CFS patients. Also, the virus shows an initial acute phase, followed by periods of reactivation. Unfortunately, none of the animals displayed any clinical symptoms. The plausible explanation is that the length of the study was insufficient, or their immune systems were not presented with a challenge, or there was a lack of a necessary herpesviral co-infection to cause disease.Fibromyalgia Researchhttp://www.blogger.com/profile/13598167140223702345noreply@blogger.com3tag:blogger.com,1999:blog-3446911767611771282.post-45005959276759176112011-01-17T17:09:00.000-08:002011-01-17T17:09:59.284-08:00British Negative Studies are Scientific FraudWhat hinders good research? Ego. Period. Simon Wessely is a good example. He has a belief - that Chronic Fatigue Syndrome is a neuropsychiatric condition. So why would he want to try and replicate the XMRV findings then - Ego. To reinforce his beliefs. How do you do this - answer: pervert the results. How do you pervert scientific findings - answer: break the rules that in order for a scientific study to be valid, you have to copy exactly. So he obtained negative results, further reinforcing his beliefs that CFS is not infectious.<br />
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But why the motive? In countries like the UK, much of the research is government funded, and the National Institute For Clinical Excellence (NICE) has a lot of control over what research goes on. In recent years, budgets have become increasingly constrained. In one of my previous posts, I mentioned about some findings on CFS that were suppressed - I directly challenge any UK bureaucrat who has access to any of these to post them on WIKILEAKS. Currently, the UK health care system has become increasingly under strain from high drug costs for biologics to treat anything from cancers, to psoriasis, rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis, and Psoriasis. For them, treating CFS would mean another huge cost factor to expand coverage of HIV drugs to CFS patients, as well as perhaps Rituximab. As long as the neuropsychiatric psychobabble can drown out the voices of good science, it is a cost they do not have to face.Fibromyalgia Researchhttp://www.blogger.com/profile/13598167140223702345noreply@blogger.com18tag:blogger.com,1999:blog-3446911767611771282.post-54046605237080409882011-01-17T16:53:00.000-08:002011-01-17T16:53:16.905-08:00XMRV Could Likely Be an emerging zoonotic diseaseRecently, a small study has revealed that ticks might be one way XMRV is passed on. The study is being done by Dr. Eva Sapi and Dr. Joe Brewer. The connection was discovered with a sample of chronic lyme disease patients showing 90% infectivity rates with XMRV and MLV's. It is coincidental that the symptoms of Chronic Lyme, and Chronic fatigue syndrome are almost impossible to differentiate. It also explains why despite antibiotic treatments, these patients fail to show improvements. Ticks are already known to carry a form of viral encephalitis. <br />
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This points to a likely zoonotic host for XMRV - XMRV could be a new emerging zoonotic disease. Figuring out the host will require the cooperation from veterinary researchers. From transplant medicine, it is already known that pigs are full of endogenous retroviruses. Deer are the primary host of ticks, although they can attach to mammals, birds, and occasionally reptiles and amphibians. A study done in Connecticut shows that lyme disease incidence dropped in proportion to deer population - a 74% reduction in deer population resulted in a 90% drop in Lyme disease in humans.<br />
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A hunter from Nevada messaged me last summer, where he denotes "In 1984, there were deer everywhere. I would see deer killed on the road daily. The following year, there was a die-off. We had gone hunting, and at the time my son was 16 - he became ill that fall, and he never got better. Six years ago, he was diagnosed with Lymphoma, and became better after aggressive chemotherapy."Fibromyalgia Researchhttp://www.blogger.com/profile/13598167140223702345noreply@blogger.com11tag:blogger.com,1999:blog-3446911767611771282.post-42815515633723352572011-01-15T22:51:00.000-08:002011-01-15T22:51:24.564-08:00HIV Drug also effective against herpesvirusesSept 23, 2010 - Institute for Research in Biomedicine - Barcelona, Spain<div><br />
</div><div>It was discovered that the drug Raltegravir (Isentress) is effective against all herpesviruses through a different mechanism than that of HIV. As it turns out, all Herpesviruses (HHV-1, HHV-2, Eppstein-Barr virus, Cytomegalovirus, HHV-8) contain the UL89 protein, which is responsible for DNA maturation. Without it, the virus cannot leave the cell to continue infection. This discovery will lead to the discovery of a class of safer drugs to treat herpesviral infections. For CFS patients, it provides a one-two punch, knocking out XMRV and Herpesvirus co-infections.</div><div><br />
</div><div>Previously, certain drugs against herpesviruses were trialled in CFS patients with only small improvements at best. The drawback to the current generation of drugs are that they are fraught with side effects. Foscarnet is extremely nephrotoxic; Ganciclovir and Valganciclovir (Valcyte) causes myelosuppresion, GI symptoms, as well as neurological symptoms; and Valacyclovir and famciclovir lack broad spectrum anti-viral efficacy. Many persons taking Valcyte report horrendous side effects, comparable to AZT. Typically, Valcyte costs $800 a month, and Isentress costs $950 a month. Raltegravir on the other hand has a very favorable side effect profile - when taken alone, it does not cause fat redistribution or raised cholesterol like other classes of HIV medications. It is rather unfortunate that very little research has been devoted to developing new classes of antiherpesvirals with better side effect profiles, since there is evidence that XMRV proliferates in EBV transformed B cells. It is also of note that B cell depletion through Rituximab provides a substantial improvement in CFS patients that lasts 3-4 months, but then returns, which leads to the conclusion that Lymphoblasts may very likely be where the secrets of CFS lie - unfortunately I do not know of any significant ongoing studies that have been conducted using bone marrow aspirations on CFS patients.</div>Fibromyalgia Researchhttp://www.blogger.com/profile/13598167140223702345noreply@blogger.com9tag:blogger.com,1999:blog-3446911767611771282.post-77018830986921470102011-01-08T20:40:00.000-08:002011-01-08T20:40:36.665-08:00Will The Li-Ka Shing Institute of Virology Score bigTwo current studies are underway at the University of Alberta - one by Dr. Andrew Mason, and the other by Dr. Lorne Tyrell and Dr. Michael Houghton (Co-discoverer of Hepatitis C virus). Dr. Mason's study is about trialling antiretrovirals, finding causation, transmission, and prevalence. The study by Tyrell and Houghton is to show cause. In a recent talk, Dr. Tyrell states that "I have suspected that CFS is a communicable viral disease since the Incline Village Outbreak at the beginning of my career, and I am confident that we are closing in fast, and excluding viral pathogenesis at this point would be utter foolishness."<br />
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For those that my not know: The University of Alberta is located in Edmonton, Alberta. Alberta boasts of a booming oilfield industry, and no shortage of revenue. The University of Alberta has been the home of several major medical milestones, and is one of the top ranked centers worldwide for molecular biology, and genomics.Fibromyalgia Researchhttp://www.blogger.com/profile/13598167140223702345noreply@blogger.com9tag:blogger.com,1999:blog-3446911767611771282.post-81489093458082288192011-01-08T20:16:00.000-08:002011-01-08T20:16:32.754-08:00Initial findings from a yet-to-be publshed studyA recent study was done to assess the pathological state in various CFS patients, healthy patients, and a handful of patients given the drugs Viread and Isentress for 3 months. All CFS patients demonstrated elevated titres of at least one of: Varicella Zoster Virus, EBV, CMV, HHV-6, and HHV-7, and one patient with HHV-8 (Kaposi's Sarcoma Associated Virus). Either or both of Mycoplasma Incognitans or Chlamydia Pneumoniae was found with alarming prevalence in CFS patients, yet was found in remarkably low prevalence in healthy individuals. In the small sample, viral titers began to fall 2 and 3 weeks after commencement of two antiretrovirals, and rapid declines in Mycoplasma Incognitans and Chlamydia pneumoniae occured after 1 month. It is of note that Mycoplasma Incognitans was once suspected of being behind the pathogenesis of CFS, and it turned out to be a false lead. Although more subtle than in HIV patients (CMV retinitis is found in HIV patients), a pattern of immune dysfunction is seen in both CFS and HIV. More news on January 17th.Fibromyalgia Researchhttp://www.blogger.com/profile/13598167140223702345noreply@blogger.com10tag:blogger.com,1999:blog-3446911767611771282.post-18641104446348454792011-01-08T19:41:00.000-08:002011-01-08T19:41:08.056-08:00New antiretroviral findings to be presented January 17thNew findings will be presented by Dr. Judy Mikovits on January 17th, at a medical conference in Santa Rosa titled "The XMRV Retrovirus and its association with cancer and neuroinflammatory diseases: The latest on research, detection, and treatment". Also, findings with antiretrovirals will be presented: the good news: almost all CFS patients showed remarkable improvements after receiving antiretrovirals - the group that received Viread and Isentress faired out best - probably owing to some of AZT's toxic side effects, the group given AZT had higher fatigue scores than those receiving Viread and Isentress. Dr. Deckoff Jones, and her daughter report that they are 75-80% better at this time.Fibromyalgia Researchhttp://www.blogger.com/profile/13598167140223702345noreply@blogger.com3tag:blogger.com,1999:blog-3446911767611771282.post-15898310948496795492010-12-27T22:17:00.000-08:002010-12-27T22:17:52.586-08:00Another retrovirus discovered at University of Alberta - Same controversy as XMRVIn the last year, there has been no shortage of controversy regarding the association of CFS with XMRV and related retroviruses. For several years, Dr. Andrew Mason at the University of Alberta has been studying the association between Primary Biliary Sclerosis, and a Betaretrovirus bearing a close resemblance to Murine Mammary Tumor virus. Much like the CFS studies, the research has been plagued by negative studies. Like the study at Whittemore Peterson Institute, the virus was visualized using electron microscopy. Like in CFS, negative studies have hampered the progress of research.Fibromyalgia Researchhttp://www.blogger.com/profile/13598167140223702345noreply@blogger.com3tag:blogger.com,1999:blog-3446911767611771282.post-49036605210573597422010-12-09T23:40:00.000-08:002010-12-09T23:40:53.548-08:00Taking on the negative studiesThe negative studies - they've sufficed at discrediting good research over the last year - several researchers are finding it difficult to get their XMRV studies published. Rather it seems who you are matters - the CDC, the Wessley group in Britain. The time has come to put politics aside, and put the issue to rest for good. There is a rule in science that in order for a confirmation study to be valid, it means copy exactly!!! <br />
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In order to do that, it would mean taking a modest amount of samples, using different methods in the same laboratory. So if we have replica A using the method described by Mikovits et. al, B using the CDC method, C using the Wessely study, and only the first method shows positivity, then contamination can be ruled out.Fibromyalgia Researchhttp://www.blogger.com/profile/13598167140223702345noreply@blogger.com4tag:blogger.com,1999:blog-3446911767611771282.post-19545935148577357482010-12-09T22:59:00.000-08:002010-12-09T22:59:26.944-08:00Testimony From a patientA patient which I will only identify by the name of Ms. X, has provided me with her account of living with CFS, and how as a desperate measure she finally found a doctor that would prescribe her antiretrovirals. Ms. X is 36 years old, and has been living with CFS since age 24. She was once a very active person - having completed the Boston Marathon one year before coming down with CFS. It all started with flu like symptoms she states, but she never fully recover until... By age 25, she would endure malaise on a daily basis - seeing specialist after specialist - two rheumatologists, a sleep specialist, cardiologist. By age 28, she would struggle to work part-time. At age 31, she was admitted to a psychiatric hospital after becoming suicidal as a result of doctors giving her the runaround. It was at this time that she was diagnosed with CFS - and she began graded exercise therapy, which left her even more fatigued. <br />
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At the time the Mikovits et. al study came out, she had been unemployed for 3 years. At this time, she began to travel around the country looking for a doctor that would prescribe her antiretrovirals - most doctors were extremely relucatant, until she found one in San Francisco that treated HIV patients early in the epidemic. She was given a two drug combination - Isentress (Raltegravir), and Viread (Tenofovir). Initially, she felt worse (Fever, chills, cough), and almost stopped taking the drugs, but after 21 days began a rapid and sustained improvement. After 3 months, she no longer experienced any musculoskeletal pain, nor any post-exertional malaise, she would return to work full time by 4 months - and currently is capable of exercising 1 hour per day. For her, the monthly cost of the combo treatment comes to a staggering $1500 a month - something she could not afford on her own, nor would any HMO or drug plan want anything to do with it - luckily for help from her family.Fibromyalgia Researchhttp://www.blogger.com/profile/13598167140223702345noreply@blogger.com14tag:blogger.com,1999:blog-3446911767611771282.post-4976520719797300422010-12-09T22:25:00.000-08:002010-12-09T22:25:55.180-08:00EBV and XMRV - a new disease modelAn unpublished Spanish study reveals what could possibly unlock the mysteries of CFS. EBV is a common herpesvirus that almost 95% of the population carries by adulthood according to the CDC, however it seldom produces disease. In a percentage of the population it causes infectious mononucleosis, but afterwards remains dormant in immune system cells. It brings the question - Could EBV or another herpesvirus be the key that unlocks the door for XMRV - quite possibly. Once XMRV enters a cell, it could quite conceivably create an immune dysfunction that allows EBV to reactivate at a low level, fuelling a vicious cycle - through EBV producing a gene that downregulates APOBEC3, somewhat like the HIV vif protein does.Fibromyalgia Researchhttp://www.blogger.com/profile/13598167140223702345noreply@blogger.com8tag:blogger.com,1999:blog-3446911767611771282.post-36001644159058743642010-12-09T22:02:00.000-08:002010-12-09T22:02:10.164-08:00A new slant on XMRVLooking at XMRV, and seeing the mention of low copy numbers, how could such a virus cause such nasty disturbances in the immune system. As a scientist, I have to take an analytical point of view - a protein called APOBEC3 has been shown to strongly inhibit retroviral replication. APOBEC3 is however only expressed in certain cells - testicular germ cells most mature blood cells in particular. However it is only expressed in low numbers, or not at all in peripheral tissues. That probably explains why it is found in such low copy numbers in blood cells and seminal plasma. However, that does not mean one should engage in unprotected sex with someone with Fibromyalgia or CFS, even though XMRV is present in low copy numbers, ***IT IS STILL INFECTIOUS***. Tonsilar tissues have been shown to be particularly prone to infection by XMRV.<br />
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Rather than simply giving up, it means we have to look elsewhere. By elsewhere means brain, nervous system, lymphatic tissues, bone marrow, tonsils, prostate, spleen, muscle. However, it would not be practical or ethical to biopsy brain or nervous tissue - which leaves the two best choices - bone marrow biopsy which can be done in a doctor's office, and muscle biopsy (in particular from tender points of fibromyalgia patients). Both can be done with a needle, with only slight discomfort.Fibromyalgia Researchhttp://www.blogger.com/profile/13598167140223702345noreply@blogger.com4tag:blogger.com,1999:blog-3446911767611771282.post-56455344060333099542010-12-09T21:44:00.000-08:002010-12-09T21:44:13.299-08:00I've returnedAfter a long hiatus, I'm back. The last year has been rather uneventful for me - I've had opportunities to pursue research, but unfortunately with the turn of events, I found that I could not undertake research that was against my beliefs. Science is fraught with politics, and they say the best scientists are those that are independent thinkers - Albert Einstein's theory of relativity was laughed at at first... Same situation is happening with Judy Mikovits. But meanwhile, I've taken on consulting work for a couple of biotech companies on contract. But I am as passionate as ever about CFS and XMRV.Fibromyalgia Researchhttp://www.blogger.com/profile/13598167140223702345noreply@blogger.com4tag:blogger.com,1999:blog-3446911767611771282.post-1634013400679512602010-01-07T13:45:00.000-08:002010-01-07T13:45:06.034-08:00Whittemore Peterson Institute Releases Official Statement on UK StudyThe Whittemore Peterson Institute has released an <a href="http://www.wpinstitute.org/news/docs/WPI_Erlwein_010610.pdf">official statement</a> regarding the recent UK XMRV study. The position of the institute is that it basically discredits the validity of the study in whole, stating it does not even qualify as a replication study. The Whittemore Peterson Institute states that they are actively collaborating with other research groups around the world, and as well Judy Mikovits stated in a <a href="http://www.nzherald.co.nz/medicine/news/article.cfm?c_id=255&objectid=10602278&pnum=1">New Zealand Herald</a> article that blood their group tested from the UK showed very similar percentages of XMRV infection in London patients as in their published study! Much like when Robert Gallo and Luc Montaigner discovered the HIV virus, other groups initially disputed their findings because they did not use the exact same methodology in their replication studies!Fibromyalgia Researchhttp://www.blogger.com/profile/13598167140223702345noreply@blogger.com7tag:blogger.com,1999:blog-3446911767611771282.post-60984166758501992022010-01-05T21:10:00.000-08:002010-01-06T14:00:59.001-08:00UK Study a Sheer Disappointment - Credibility of Replication Study QuestionableIt has come to my attention, and I have read the research article "Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome" in the publication PLOS one. I have studied the facts behind the research, which I find rather unremarkable at first glance. However it has come to my attention from Dr. Suzanne Vernon's analysis that different primers were used, collection methods varied from the Whittemore-Peterson study, different methods were used to purify genomic DNA and amounts differed, and PCR amplification methods were different. The fact that a different polymerase was used could skew the results altogether, fouling the results - the golden rule in replication studies is copy exactly!!! What I did find remarkable however, is who is behind the research - noting the psychiatric connection: Institute of Psychiatry, King's College London - and none other than Simon Wessely - Britain's own version of Dr. Reeves - which pours some cold water on the credibility of this study - statements issued by Wessely stating his opinion before the experiment was done, and the speed in which it was done indicates it was not a good quality study. Before any conclusions can be reached, I would like to see the results of the ongoing study by Dr. Kerr, which in my opinion should bear a significant amount of credibility, as should the Swedish study by Dr. Jonas Blomberg.<br />
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I would hope that the Whittemore Peterson Institute will retest the samples in this study, and establish whether or not experiment protocol was followed - meanwhile it's a waiting game for results of other studies. Hopefully ME/CFS patients will not be forced to hear that neuropsychiatric psychobabble much longer - and the only way the truth behind ME/CFS will be known is through generously funded, high-quality studies.Fibromyalgia Researchhttp://www.blogger.com/profile/13598167140223702345noreply@blogger.com11tag:blogger.com,1999:blog-3446911767611771282.post-63221237901666016172009-12-21T16:57:00.000-08:002009-12-21T16:57:51.480-08:00News on Important New Studies UnderwaySince the initial findings of the link between XMRV and ME/CFS became public in October, a flurry of new research has ensued. The study at the top of the list is currently underway at Uppsala University to try and replicate the findings of the Whitemore Peterson Institute in Swedish patients. The study is very well organized, however it's findings could be a mixed blessing: XMRV findings may be different in European cohorts, meaning that other closely related retroviruses might be discovered if new studies are pursued. Dr. Jonas Blomberg's real-time PCR assay might just be what is required to find these viruses.<br />
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Another study is currently underway to determine the atomic structure of XMRV protease at one center. This study was initiated after a link was made to XMRV in certain prostate cancer cell lines. Crystals of the protein have been grown, however this is only a first step: heavy metal derivatives must be produced, and crystals must be found that will diffract to a sufficient resolution to obtain useful data for drug development - a process that is still months away.<br />
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Another study is currently getting underway at Cornell University that will seek to determine retroviral diversity in ME/CFS patients, and try and correlate the findings with functional status in CFS patients. The project is being done in collaboration with the Whitemore-Peterson Institute and the Columbia University Center for Infection and Immunity. <br />
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Another study is getting underway at Instituto de Biologia Molecular en Medicina y Terapia Genica, Universidad de Guadalajara to determine if infecting peripheral monocyte cell lines in culture with XMRV alters the 2-5A synthethase/RNASE L pathway, and the resulting differential cytokine expression. I don't understand spanish, so it would be appreciated if someone who does could dig up more information for me!Fibromyalgia Researchhttp://www.blogger.com/profile/13598167140223702345noreply@blogger.com6tag:blogger.com,1999:blog-3446911767611771282.post-60519677123775204762009-12-21T15:49:00.000-08:002009-12-21T15:49:19.426-08:00Fellow Britons Unite For The Truth!It has come to my attention as of late that our government <a href="http://www.meactionuk.org.uk/The-MRC-secret-files-on-ME.pdf">holds a file</a> in the National Archives at Kew, which contains MRC documentation on ME since 1988. The file was to be kept from the public eye until 2023, however this has been extended until 2071! Normally, such measures are only enacted on matters of defence, national security, and in matters that are considered very confidential. But what on earth would the medical research council want to keep from public view??? It comes from the same time as the UK's own version of Dr. Reeves - Simon Wessely began to propagandize ME as a psychiatric illness. It would seem rather absurd to even cite patient confidentiality, as a black marker would make short work of maintaining patient confidentiality.<br />
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However, fellow Britons, you have options. In <a href="http://www.nationalarchives.gov.uk/catalogue/displaycataloguedetails.asp?CATID=-5475665&CATLN=7&Highlight=&FullDetails=True&j=1">THIS</a> document, there is a <a href="http://www.nationalarchives.gov.uk/contact/form/generalcontactform.asp?id=15&action=1&DOCREF=FD%2023/4553/1">LINK</a> to request a review of the record under the Freedom of Information act, which requires the filling out of only a few fields. If the National Archives does not provide a satisfactory response, then contact the parliamentary and health services ombudsman:<br />
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The Parliamentary and Health Service Ombudsman<br />
Millbank Tower<br />
Millbank<br />
London, SW1P 4QP<br />
Telephone: +44 (0) 84 5015 4033<br />
Fax: +44 (0) 20 7217 4000<br />
Email: <a href="mailto:phso.enquiries@ombudsman.org.uk">phso.enquiries@ombudsman.org.uk</a><br />
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You may also want to contact:<br />
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Secretary of State for Justice and Lord Chancellor<br />
Selborne House<br />
54-60 Victoria Street<br />
London SW1E 6WQ<br />
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Also, if the requested information is refused, an application may be made to the Information Commissioner, who has the power to order such disclosure, and if unsuccessful, the applicant may appeal the decision to an appeal tribunal - in many cases which have been successful the information has been provided with some redactions to protect confidentiality: The appeal tribunal consists of experienced barristers or solicitors which must provide a fair and independent review. It is your right, and I strongly recommend that you exercise these rights!Fibromyalgia Researchhttp://www.blogger.com/profile/13598167140223702345noreply@blogger.com6tag:blogger.com,1999:blog-3446911767611771282.post-12035201563198513942009-12-08T13:55:00.000-08:002009-12-08T13:55:07.820-08:00Male CFS Patients May Have OptionIn recent studies, it has been shown that DHT (dihydrotestosterone) increases XMRV replication rate threefold. This is not surprising, considering that a number of prostate drugs target this very hormone. Testosterone is metabolized to DHT, which is more powerful - but it is also implicated in pattern baldness, prostate problems, and excess body hair. Some drugs such as Casodex and Flutamide will block DHT at its receptor, however they will result in impaired fertility, loss of libido, and feminization effects, as testosterone is necessary to mitigate the effects of estrogen.<br />
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On the other hand, blocking the conversion of Testosterone to DHT should result in a significant drop in viral replication rate. There are 2 very safe drugs that I can think of that can attain this effect: Avodart (dutasteride), and Proscar (available as Propecia in a lower dosage form). A threefold drop in viral replication rate could have a significant effect on symptoms of ME/CFS - It is my opinion that at a certain threshold, the immune system is capable of keeping XMRV in check, hence why XMRV is found in a small number of healthy controls. I would like to see a clinical trial enrolling male patients to test this hypothesis. The effects of these drugs have negligible effects on male fertility - treatment will only produce mild reductions in sperm count averaging 6%. Serum testosterone increased considerably, which is necessary for muscle protein synthesis, regulating the hypothalamus-pituitary axis, and increasing mental and physical energy - all things ME/CFS, Fibromyalgia, and Gulf War Syndrome patients could stand to benefit from.Fibromyalgia Researchhttp://www.blogger.com/profile/13598167140223702345noreply@blogger.com21tag:blogger.com,1999:blog-3446911767611771282.post-9752391395789873862009-12-07T20:44:00.000-08:002009-12-07T21:06:03.175-08:00CDC Damage Control: ME/CFS Research Group Relieved of DutiesIn a stunning move, responsibility for XMRV research has been taken away from the ME/CFS working group within the CDC, and re-assigned to the division of HIV/AIDS prevention. This group will be in charge of replicating findings of the Whittemore-Peterson Institute, rather than the group under the control of Dr. Reeves. The move is highly significant: it appears that the CDC is now acknowledging the serious nature of XMRV.<br />
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The CDC will be part of an interagency working group on XMRV, led by Dr. Jerry Holmberg. A three-part study will be initiated:<br />
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<ol><li>The first part will consist of standardizing and validating laboratory methods and reagents for XMRV testing. This stage will use samples provided by samples collected by Dr. Judy Mikovitz. The intention is to create an FDA approved test.</li>
<li>The second part will test a much larger sample than the initial study, trying to determine the prevalence of XMRV in the general population, and the blood supply.</li>
<li>The third part will consist of how XMRV is transmitted, how it causes disease, and how it affects various subgroups of the population.</li>
</ol><div>The forceful demotion of Dr. Reeves is a sign that the CDC is in damage control mode. The HIV/AIDS prevention group in the CDC has many capable retrovirologists, who can provide years of expertise. In my opinion, this turn of events should lead to balanced, common sense research.<br />
</div>Fibromyalgia Researchhttp://www.blogger.com/profile/13598167140223702345noreply@blogger.com36tag:blogger.com,1999:blog-3446911767611771282.post-63470623630127471272009-12-07T00:51:00.000-08:002009-12-07T00:51:43.149-08:00Apricitabine May Be Effective Against XMRVApricitabine, an NRTI structurally related to lamivudine, may provide activity against XMRV Reverse transcriptase. XMRV, like the drug resistant strain of HIV-1 contains the M184V substitution, explaining why it is succeptible to AZT and not 3TC (lamivudine). The FDA has granted fast-track approval to the drug, meaning it should be available some time next year. It appears to be extremely well tolerated, and was not associated with abnormal blood lipids, liver or kidney toxicity, or bone marrow suppression.Fibromyalgia Researchhttp://www.blogger.com/profile/13598167140223702345noreply@blogger.com5tag:blogger.com,1999:blog-3446911767611771282.post-17139887001112017182009-12-06T22:39:00.000-08:002009-12-06T23:08:43.188-08:00Antiviral Study Shows Few Options<span style="font-family: 'Lucida Grande'; font-size: small;"><span style="font-size: 11px;"><br />
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A new Study released by Sakuma et. Al this week, provides groundbreaking new information on therapies for XMRV. The results are not good: 10 licensed HIV-1 anti-virals were tested - only 1 showed strong activity, and 1 showed weak activity. Out of the RTI's, AZT, 3TC, Tenofovir, D4T, Efavirenz, and Nevirapine were tested - only AZT showed strong activity. Previously I reported that 3TC and Emtricitabine showed activity against a closely related virus: 3TC has negligible activity against this beast, and Emtricitabine remains untested. The mechanism for 3TC resistance is likely a Valine substitution at position 184, in place of a methionine. Emtricitabine, Abacavir, Etravirine, and Zalcitabine remain untested. Three protease inhibitors were tested: Ritonavir, Indinavir, and Saquinavir: Only Ritonavir demonstrated weak activity at high concentrations - something that was not unexpected. One experimental integrase inhibitor was tested: the compound 118-D-24 which was ineffective, good news is that it is structurally distinct from Raltegravir, and 118-D-24 does not inhibit MLV integrase either.<br />
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A comparison of the sequences reveals some astonishing details: the XMRV Reverse-Transcriptase resistance mechanisms are astonishingly similar to HIV mutations: Valine at position 75 is substituted with Glutamine (d4t resistance), Lysine at position 103 substituted with Serine (Efavirenz resistance), A Valine at position 106 is substituted with Tyrosine (Nevirapine resistance), A Methionine at position 184 is substituted with Valine (3TC resistance). A closer examination reveals another stunning detail - most other drugs targeting Reverse-transcriptase are not likely to work, as the mutations giving rise to their resistance in HIV are apparent in XMRV. The only good news is that XMRV does not foster the critical 4 amino acid mutation giving rise the Multi-nucleoside analog resistance. Raltegravir still holds promise, as XMRV integrase bears a close sequence homology to MLV integrase.<br />
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Certainly, it is not a good situation. The toxicity of AZT leaves a lot to be desired - HIV have much more tolerable Reverse transcriptase inhibitors at their disposal. The development of drugs effective against XMRV has to essentially start from scratch - determining X-ray structures of XMRV Reverse Transcriptase, Protease, and integrase, modeling candidate molecules, conducting clinical trials, and seeking FDA approval. The sequence differences of XMRV reverse-transcriptase will provide incentive for HIV drug research - the differences are what also gives HIV-1 resistance to current therapies. We are basically where we were in 1987 with HIV - with Didanose (ddl) being only the second HIV drug to follow 4 years later. <br />
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This study only reinforces the urgency of kicking XAND research into high gear - 18 years were lost due to what I call criminal negligence at the CDC, and I am not afraid to call it the worst medical fraud of all time - only the CDC and their research cronies would stand to benefit -- not the patients, not the drug companies, not HIV patients, and not the doctors. If the findings of Defreitas had been properly handled, patients with neuroimmune disorders would have options, and HIV patients would have drugs to treat resistant HIV strains.<br />
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<div style="font: 8.0px Times; margin: 0.0px 0.0px 0.0px 0.0px;"><span class="Apple-style-span" style="font-size: medium;">Sakuma, R., et al., Xenotropic murine leukemia virus-related virus is susceptible to AZT, Virology (2009),</span><span style="font: 12.0px Helvetica;"><span class="Apple-style-span" style="font-size: medium;"> </span></span><br />
</div><div style="font: 8.0px Times; margin: 0.0px 0.0px 0.0px 0.0px;"><span class="Apple-style-span" style="font-size: medium;">doi:10.1016/j.virol.2009.11.013</span><br />
</div>Fibromyalgia Researchhttp://www.blogger.com/profile/13598167140223702345noreply@blogger.com8tag:blogger.com,1999:blog-3446911767611771282.post-30444265866943489342009-12-06T18:51:00.000-08:002009-12-07T20:21:42.157-08:00Two new Studies: Part I - Co-infections point to three strikes theoryA follow-up study was done by Dr. Kerr, demonstrating that ME/CFS symptoms are not caused by XMRV alone, but that co-infections have various additive symptoms - leading more credence to what I call a three strikes theory. For ME/CFS to develop, you need the following three conditions to develop in a more/less orderly sequence:<br />
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<ol><li>Infection with XMRV</li>
<li>Co-infection with another etiological agent: various herpesviruses, certain bacteria</li>
<li>Major immune challenge: Influenza, surgery, immunosupression</li>
</ol><div>The basis of this research is that Dr. Kerr separated various CFS cohorts based on symptoms, and tested various consistent immunological disturbances based on certain pathogens present. There was a definitive correlation between the severity of symptoms, and the type of infection present. The four pathogens tested were: Eppstein-barr virus, enterovirus, parvovirus B19, and the bacterium <i>coxiella burnetii</i>. In the test, a study was done looking at the differential expression of 88 genes. There was also a regional difference in CFS subtype patterns: Birmingham, Bristol, Leicester, London, New York, and Dorset.<br />
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Here are my conclusions without getting into too much detail: even though EBV, Parvovirus B19, and Enterovirus have been fingered as triggering ME/CFS, it clearly tells me that they are not the cause. ME/CFS has often been described as a heterogenous ailment of many possible causes: a theory that existed in AIDS patients before the discovery of HIV. I believe that ME/CFS, FMS, and Gulf War syndrome bear a single unified cause, and that cause is XMRV.<br />
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XMRV is the first strike: without XMRV or closely related retroviruses you can't have ME/CFS. If XMRV infects a normal individual, I am of the opinion that a healthy immune system can keep the virus in check for many, many years. Over time, XMRV leads to an immune dysfunction syndrome, though not a severe life-threatening immune deficiency syndrome like AIDS. XMRV is the mastermind.<br />
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The second stage, which I call the second strike, is what sets the stage for ME/CFS. Throughout a lifetime, most of us will become infected with multiple persistent herpesviruses: EBV, HHV-6, Cytomegalovirus, Herpes Simplex... yet a healthy immune system can keep them in check. At this stage, most XMRV infected individuals will probably remain asymptomatic. The body now struggles to maintain the immune system at equilibrium, and it might take longer to recover from simple viruses like the common cold, and some patients might exhibit sub-clinical signs of ME/CFS. The pathogen in this case plays the role of accomplice.<br />
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The third stage I will loosely call the third strike - the event that initiates ME/CFS I believe requires a period of prolonged immune activation, or inversely immunosuppression. At this point, the immune system is ill-prepared to fight a war on another front. In comes a pathogen that causes a vigorous and prolonged immune response such as a bacterial infection, or influenza, and now the immune response is mobilized towards it, retreating from the two previously acquired infections: the viral burden initiates a chain reaction within immune cells. XMRV viral load spikes, leading to the destruction of NK cells, and pathogens like EBV now seize the day, and begin replicating, and viruses like EBV can now cause immune downregulation, slowing the creation of new NK cells from progenitor stem cells, capable of arresting EBV. <br />
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Conclusion: ME/CFS, FMS, and Gulf war syndrome are caused by a common pathogen, which causes a common set of symptoms, and the heterogenous cluster of symptoms can be explained by co-infections with other pathogens.<br />
</div>Fibromyalgia Researchhttp://www.blogger.com/profile/13598167140223702345noreply@blogger.com6tag:blogger.com,1999:blog-3446911767611771282.post-61565368588749168452009-12-02T16:53:00.000-08:002009-12-02T16:53:46.757-08:00Ampligen "Death Blow" Another Tragedy for CFS SufferersIn a shocking move, the FDA yesterday refused to approved Hemispherx's drug Ampligen. It represents a devastating blow for Hemispherx who have in vain attempted to garner approval for Ampligen for over 20 years. In their response letter, the FDA essentially demands that Hemispherx begin their clinical trials from scratch. They site initial clinical trials fail to convince the review panel of Ampligen's efficacy, and that new clinical trials be conducted testing different doses for at least six months, on at least 300 patients, compared to the previous study which enrolled just 230 patients. The FDA also goes on to cite unresolved manufacturing problems. Considering that the previous study took 6 years to complete, approval doesn't appear likely any time soon, and likely won't be approved in other jurisdictions, as other nations have followed the guidance of the FDA, with a handful of exceptions of drugs that have gained approval by the European Medicines Agency before FDA approval is granted.<br />
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For persons suffering from ME/CFS, FMS, and Gulf War Syndrome it shows that government agencies continue to recognize these conditions as a real illness. And research dollars earmarked for CFS/ME research gets misappropriated by CDC bureaucrats as a slush fund, where not one meaningful study has come out of it. And it appears recent developments have not shifted the groupthink mentality of the CDC - but it will come a time when they will find themselves standing pretty well alone if replication studies on XMRV are in line with those of the Whittemore-Peterson institute, which I have reason to believe will be.<br />
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I believe that psychologically Ampligen represents a huge setback, but in the end it will amount to no more than a bump in the road. Tests on antiretrovirals are going ahead full steam in pharmaceutical labs as we speak, and I've dug up a couple of other compounds that have demonstrated activity against other retroviruses: Lamivudine and emtricitabine - both have a far greater safety profile than Zidovudine (AZT), posing a low risk of anemia, nephrotoxicity, hepatoxicity, and pancreatitis. I'm not particularly fond of Non-nucleoside Reverse Transcriptase inhibitors, due to their unfavorable side effect profile - distressing rash in as much as 20% of patients, and severe liver damage seen with Nevirapine and Etravirine - making patient compliance and adherance to treatment an issue in itself. I also don't favor a single drug regiment - I would like to see a combination pill of either Lamivudine or Emtricitabine with raltegravir.Fibromyalgia Researchhttp://www.blogger.com/profile/13598167140223702345noreply@blogger.com3