looking_for_a_cure_for_me nomme wishing for wellness Research into M_E hit by cash crisis DR JOHN GOW is leading the ground-breaking research on the illness ME at Glasgow University PIONEERING research by Glasgow scientists which could lead to a cure for ME is under threat from a lack of funding. A team at Glasgow University has made a genetic discovery which could change the lives of patients with the debilitating condition. But the ground-breaking work - which is a year from completion - will halt within weeks unless extra cash is found. Dr John Gow, leading the research, said: "As it stands I will not be able to continue my research beyond the end of May. "I face having to let my research assistant go by then, which means the team will be broken up and momentum with the research will be lost. "It would be a great loss for the university and for ME patients." His plight has been taken up by Alex Fergusson, Tory MSP for Galloway. Mr Fergusson said: "It's entirely unacceptable that the Executive seems prepared to see this grind to a halt, when we may be just a year away from a life-changing diagnostic test and cure for ME." Dr Gow believes ME is caused by a gene malfunction which prompts the immune system to "work overtime", making patients excessively tired. He says a cocktail of drugs could be used to switch off the defective genes, allowing patients to lead normal lives. The drugs have still to be tested but Dr Gow believes his research is a big step forward. He is waiting to hear about an application for an additional grant. Dr Neil Abbot, of ME charity Merge, said Dr Gow's work was "absolutely crucial" and called for more funding for it. Dr Gow's funding comes from the Executive via Scottish Enterprise. A Scottish Enterprise spokeswoman said: "This could be an exciting opportunity for Scotland and in 2003 we offered an award to Glasgow University to develop this technology further. "The project is at an interesting stage of its development and we continue to work with Glasgow University to try to help it achieve a commercial outcome." TIMESFILE •ME (Myalgic Encephalopathy) is also known as Chronic Fatigue Syndrome, Post Viral Fatigue Syndrome and Yuppie Flu. •Symptoms include extreme tiredness, muscle pain, sensitivity to noise and light, severe headaches, digestive problems and disturbed sleep patterns. •ME is notoriously difficult to diagnose. Doctors arrive at a diagnosis by a process of elimination, which can take up to six months. •ME can last for anything between a few months and many years. •As no cure exists, treatment involves managing the condition by finding a balance between activity and rest. •For years it was debated whether ME was really an illness. It finally gained full medical acceptance in 2002. http://www.eveningtimes.co.uk/hi/news/5039240.html Fri 20 May 2005 Scottish scientists find 'key to curing ME' IAN JOHNSTON SCIENCE CORRESPONDENT A REMEDY for the debilitating condition ME, once derided as "yuppie flu", could be available in as little as a year after groundbreaking Scottish research. A Glasgow University team has discovered a malfunction in sufferers' genes which appears to prompt their immune system to "work overtime", making patients extremely tired. The lead scientist, Dr John Gow, said a cocktail of drugs could be used to "turn off" the genes, allowing patients to live "a fairly normal" life. The university has already patented the genes involved as a means of diagnosing the condition, also known as chronic fatigue syndrome (CFS), quickly and cheaply. The disease has gradually gained acceptance and in 2002, Professor Sir Liam Donaldson, the chief medical officer for England and Wales, said that "CFS/ME should be classed alongside other diseases such as multiple sclerosis and motor neurone disease". Dr Gow, a senior lecturer in clinical neuroscience at the university, mapped all 33,000 genes in CFS sufferers and then compared them with the genes of healthy people. Dr Gow, who works at Glasgow's Southern General Hospital, said they found CFS sufferers had a particular kind of "unusual gene expression". "This means the genes are switched on or off at an inappropriate time. We have identified a number of genes that are wrongly switched on," he said. "It looks like the immune system is working overtime when it shouldn't be, making the patient tired." Every cell in the body contains the same 33,000 genes, but only about 10 per cent are actually doing anything at any one time. There are genes related to the production of liver proteins in brain cells, for example, but these should be "switched off" because liver protein is not required in the brain. Drugs can be used to control chemical pathways that act on the genes and Dr Gow said he had identified ones that could be used to regulate the over-active genes in CFS. These drugs are already on the market for other conditions and could be given to CFS sufferers within a year if tests prove positive. Dr Gow stressed that the drugs had to be tested in practice. "This is not a major breakthrough yet, but it is a big step forward," he said. A prototype diagnostic testing kit has already been developed which would give doctors "a yes or no answer" about whether someone had the condition. Currently it takes about six months to make a diagnosis. However, Dr Gow said he was currently "going nowhere" because his funding had run out. Dr Neil Abbot, of medical research charity Merge, which works on ME, said: "This is very exciting work. The analysis of genes is one of the most interesting modern areas of research which has the potential to come up with a cure, but this may be in the long term." John Breward, 51, of Bruntsfield in Edinburgh, contracted ME after a severe case of viral pneumonia 20 years ago. The former research scientist is now housebound and on bad days bedridden, suffering from extreme exhaustion, pain in his muscles and joints and migraine-like headaches. "The possibility of a cure... that would be absolutely wonderful," Dr Breward said. "We have had false dawns before with people saying they've diagnostic tests and treatments which haven't panned out - so I'm cautiously optimistic." TAKING ACTION LYNNE Mackay loved swimming and skiing and never missed a day at school. But at 13 she changed: she languished in bed, missed entire weeks of school and was prone to sudden tantrums. The reason for this transformation was unclear - she was close to being expelled - until she was finally diagnosed as suffering from ME. Lynne, now 16, who lives in Penicuik near Edinburgh, said the prospect of a diagnostic test and even a cure for ME was exciting. "I was ill all the time, but people thought I was making it up to get attention or get off school, so to get the diagnosis was just amazing, really. Then you know it's not just in your brain and you're not going mad," she said. She has learned not to exert herself too much and this enabled her to continue her schoolwork. She is studying for eight Standard Grade exams. "My symptoms are very mild now. I used to get lots of headaches, earache, sore throat, feel very tired, aching muscles and flu-like symptoms," Lynne said. "It just drains you. I didn't want to do anything, couldn't do anything. But I've learned to pace myself. I have had to not sleep during the day and keep my sleep patterns regular. "If I feel a wee bit tired to do something, I don't do it. If I did, I know it will push me back. "I'd been a really active kid. I don't really want to sit around and do nothing. I don't want to watch a DVD on my bed - I want to go out and muck around with my friends. You have to learn to take a step back, but there's always a chance of a wee infection that will knock you back." http://news.scotsman.com/scotland.cfm?id=550752005 050527 ... megan i apparently make everything about me and i don't know how to stop worrying and i don't know how to stop missing your arms or your voice at the nape of my neck and i just can't figure out how to make you fall in love with me again... just to have you want to sit and talk with me again or lay and look at the sky or walk or anything for that matter just you and me 050527 ... somenom http://www.meactionuk.org.uk/Gow_Research_Appeal.htm has an abstract of the research 050528 ... somenom "Scientists 'unlock ME genetics' Scientists have identified thousands of genes which appear to play a role in chronic fatigue syndrome (CFS). A team from Glasgow University found a particular pattern of genetic activity among 50 people with the condition. They hope their work, which is still in its early stages, could lead to a diagnostic test and new treatments. CFS - or myalgic encephalomyelitis (ME) - used to be dismissed as "yuppie flu" and has been widely recognised as a disease only in recent years. Gene signature Lead researcher Dr John Gow said: "It is another year's development before it becomes an accepted diagnostic test and, similarly, we need to do some trials with therapy before that becomes widely available. But it is exciting." By looking at the whole genome of about 50 people with chronic fatigue syndrome, they discovered certain genes that were different to those seen in healthy people of a similar age and sex. We think we can find drug treatments that will be beneficial to patients Dr Gow Dr Gow said: "We have identified genes which were up-regulated compared with genes in normal healthy individuals, suggesting we could possibly have a diagnostic test for this syndrome which doesn't exist at the moment." But he said they needed to check that this "gene signature" was specific for chronic fatigue syndrome by looking at more people with the condition, which would take a year or so. Colleagues at the same university are also looking at targeting treatments towards the faulty biochemical pathways caused by the overactive genes in chronic fatigue syndrome. Future hope These drugs are already on the market for other conditions, so if they are proved to be useful in chronic fatigue syndrome, they could be given to patients in the near future. "Our work has given us clues as to which pathways are up- or down-regulated and we know which drugs activate different pathways, so we think we can find drug treatments that will be beneficial to patients," Dr Gow said. "Having said that, it really needs to go through proper trials before these drugs become widely available." A spokesman from Action for ME said: "We are very interested to know and explore more." He said it was good that work such as this was being carried out into chronic fatigue syndrome." http://news.bbc.co.uk/1/hi/health/4580051.stm 050529 ... the above article dated: Saturday, 28 May, 2005, 23:04 GMT 00:04 UK) 050529 ... skyburst777 San Francisco Chronicle From Skepticism to Science After 20 years, chronic fatigue syndrome may finally be getting some respect and cutting-edge science Dorothy Wall Sunday, June 5, 2005 "It was 1984 when Dr. Carol Jessop, then an associate professor in the department of internal medicine at UCSF, first saw the patient she would never forget. A 40-year-old businesswoman who had always been healthy and active came to the clinic with a bizarre story. While driving on the freeway, she was suddenly hit by such overwhelming nausea and fatigue she had to pull over. "It was dramatic," remembers Jessop. "I'd never heard anything like this before, that sudden. This woman absolutely felt drained and near collapse." The mystery quickly deepened. Jessop drew some endocrine labs, checked the woman's cortisol level, looked at her CBC (complete blood count), and "low and behold, everything comes back totally normal. And she's getting worse by the time I see her in follow-up. Now she's aching all over, has some baseline headaches, she's not sleeping well, and she just feels like she's caught in a flu." Concerned, Jessop consulted with a colleague in infectious disease at the university, and talked with another in endocrinology. Within the month, a couple more patients had come in with similar stories of overwhelming malaise and fatigue, muscle aches, confusion and concentration problems. "A lot of my colleagues said that these people must just be depressed. Put them on tricyclic antidepressants," reports Jessop. "I definitely felt that there was some criticism of my work and my attempt to try and uncover what was going on." But Jessop persisted. "I was clear in my head something was happening, and I was willing to look in every direction." By 1986, she was seeing more than 300 patients with the now-familiar symptoms, and cluster outbreaks had been reported in cities and towns across the country, including a well- publicized one at Lake Tahoe. She consulted with UCSF virologist Jay Levy, who was then working to discover the HIV virus. She and Levy wondered whether they were seeing a new virus or something related to AIDS in a milder form. Somehow, they felt, the immune system in these patients had been disrupted. When we get sick with a flu, the fever, achiness and fatigue are not caused by the virus itself but by the immune response, the chemicals released to fight infection. Perhaps Jessop's patients had an immune system stuck in the "on" position, creating persistent flulike symptoms. But what virus was causing the disruption? After investigating a number of potential culprits -- human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV), among others -- Jessop and Levy, like other investigators, came up empty. In 1988, the Centers for Disease Control and Prevention (CDC) named the puzzling illness chronic fatigue syndrome (CFS), as if this illness were about nothing more than being a little extra tired. The moment the name was set in print, patients lambasted it for trivializing a devastating illness and inviting psychiatric stigma. By 1991, Jessop was seeing 1,500 patients with CFS, marking the Bay Area as one of the largest clusters of the nationwide epidemic. Most of these patients had been ill for years -- some bed- or housebound -- many were unable to work. Yet without a known cause or laboratory evidence of abnormalities, the illness continued to be subject to psychiatric explanations by physicians, disbelief by family and friends of those who were ill and media ridicule as the "yuppie flu." It has been a long journey from those early days when only a few renegade physicians like Jessop took this illness seriously. After two decades of dogged advocacy work by patients and a handful of concerned physicians and researchers, the facts about CFS are coming to light. Today CFS -- also called chronic fatigue and immune dysfunction syndrome (CFIDS) and myalgic encephalomyelitis (ME) -- is known to be a serious and disabling illness affecting an estimated 800,000 adults in the United States, although it appears that only 10 to 17 percent of these cases have been diagnosed. Studies by the CDC show that people with CFS can be as impaired as someone with heart disease, cancer or multiple sclerosis and that CFS costs the economy $9.1 billion a year in lost productivity. Two to five times as many women as men have the illness, and contrary to popular myth, minorities and people at lower socioeconomic levels are at higher risk for CFS. Most medical textbooks now have a section on CFS, and though the great majority of physicians say they feel inadequately informed about the illness, many want to know how they can help their patients. Jessop reflects on the change. "I think today, physicians have studied fibromyalgia, have studied CFS, and many of them are more comfortable saying, 'OK, we don't know everything about it, but let's talk about what we can do.' " While the cause is still unknown, the search for a single virus no longer occupies most researchers. Most now suspect CFS has a variety of triggers, alone or in some combination: one or more pathogens, chemical and environmental exposures, stress or injury and genetic predisposition. Whatever the initial provocation, the autonomic, immune and neuroendocrine systems become dysregulated, producing the constellation of symptoms: overwhelming fatigue, post-exertional malaise, muscle and joint pain, sore throat, swollen lymph glands, light and sound sensitivity, headaches, "brain fog" and cognitive problems. Like Jessop, pediatrician David Bell saw a cluster of patients with what looked like a severe viral illness in his clinic in Lyndonville, N.Y., in 1985. He and his wife, Karen, an infectious disease specialist, at first considered everything from typhus to Rocky Mountain spotted fever to Q fever. They, too, suspected an infectious origin, but couldn't find a specific bug. And they, too, encountered disbelief from other specialists they consulted. Says Bell, "The specialists wrote back and said that these kids are all neurotic and they're just exaggerating the symptoms, which I knew couldn't possibly be true. " After treating and studying CFS for 20 years, Bell has a clearer picture. "I see this illness as a post-infectious dysautonomia [autonomic nervous system dysfunction]. ... What that means is that an infection initiates a process whereby the immune system starts overreacting. And that process then causes reduction in cerebral blood flow, abnormalities in the HPA axis [a key part of the endocrine system] and a variety of other things." Bell's description of a possible disease process in CFS reveals the complexity of this illness: an immune system that is overreacting, reduced blood flow to the brain, defects in the autonomic system that controls heartbeat and blood pressure, abnormalities in the endocrine system regulating production of hormones. Multiple things are going wrong in the body of a person with CFS, one affecting another in a cascade of interactions. Adding to the complexity, the disease process may not be the same in all people with CFS. Just as a painful, swollen joint can be caused by infection, injury or arthritis, the symptoms of CFS may be the end result of different processes. Researchers are recognizing the importance of subtyping patients -- perhaps by similar symptoms or illness history, or by the predominant organ systems involved -- to make both treatment and research more effective. One of the biggest obstacles to understanding CFS has been the absence of a "big picture" view, and this absence is directly tied to lack of federal research money. Until recently, most CFS studies have been small, often funded by patient advocacy groups, and narrowly focused. One study of 36 subjects might document difficulty with multitasking; another study of 121 people with CFS shows they have low levels of the hormone cortisol. Like many, Bell is angered by the lack of federal investment in research. "The amount of money being spent on research is trivial. I mean, it's so small that it just doesn't count when you compare it to other illnesses affecting huge numbers like this is." According to its own documents, the National Institutes of Health (NIH) in 2003 spent $99 million on multiple sclerosis and $6 million on CFS, though CFS affects twice as many people. Bell adds, "And a lot of that $6 million was spent on fatigue independent from chronic fatigue syndrome." Adding insult to injury, documents released under a Freedom of Information Act request made by CFS advocates revealed that between 1995 and 1998, the CDC spent $12.9 million allocated for CFS on other projects, and misrepresented its spending to Congress. Under intense pressure from patient advocates, particularly the CFIDS Association of America, the largest patient advocacy group, the CDC restored the misallocated funds, mostly in fiscal years 2002 and 2003, and finally started a major research effort. Federal funding for CFS research -- from both the NIH and the CDC -- was still only $16 million in 2003, according to the CFIDS Association, and today is on the decline. Nonetheless, the current federal undertaking is significant. The CDC's main goals are to understand whether CFS is one disease or many, to define its natural history and clinical presentation, to educate health care providers and to identify the pathophysiology (disease process), causal agents and risk factors. There's been quite a buzz about several studies under way. Bell's voice rises with enthusiasm when he describes them. "One was the Dubbo study by the CDC. Extraordinary study. Wonderful science. What they're doing is, in the county of Dubbo, Australia, they're prospectively looking at all cases of Epstein-Barr virus, Ross River virus and Q fever, illnesses known to sometimes have a chronic aftermath. And they are now seeing that 10 percent of these people go on to develop chronic fatigue syndrome. ... This is implying that those three infections cause CFS in otherwise healthy people. That's very interesting. "The other study ... that just knocked my socks off was hepatitis C. This was a study done by a hepatitis specialist who was treating hepatitis C with interferon," a protein that is part of the body's antiviral response. ... "Seventy percent developed marked fatigue, and 30 percent developed chronic fatigue syndrome. So it was the interferon treatment that caused the CFS, not the actual virus circulating in their system. ... The CFS is the immune response from an infection." This finding is consistent with the idea that the symptoms of CFS could be precipitated by an immune system in overdrive. A key component of the CDC research effort is the use of microarray technology to analyze the genetic material of a person with CFS. Researchers take a sample of blood or tissue; apply it to a glass slide, called a "microarray," which contains more than 20,000 gene identifiers; and are able to determine which genes in the sample are being "expressed," that is, turned on or off, or turned up or down. This gene expression profile provides a window into the disease process. Microbiologist Suzanne Vernon, team leader of the CDC's molecular epidemiology program, explains: "We're using very exploratory molecular technologies to try to understand what is wrong in people with CFS. We've tried to focus on discovering biomarkers that help us to further understand the pathophysiology of CFS and also to perhaps identify diagnostic markers." Since 1988, CFS has been diagnosed based on a patient's symptoms and by ruling out other illnesses that can cause chronic fatigue. Finding a diagnostic marker, a measurable biological abnormality that appears in all people with CFS, would be an important step forward. In preliminary work, Vernon's team has been able to use microarray technology to distinguish between people with CFS and healthy controls. More recently, they've been able to show differences among people with CFS, confirming that CFS is a heterogeneous illness. Examining 3,800 genes in 23 women, they found that those with sudden-onset illness (developing in one week) had a different gene expression profile than those with gradual onset (developing over several months). With further study, researchers hope to find a common pattern or signature of gene expression that appears in all people with CFS. They may find particular patterns that are specific to subgroups as well. Eventually, the microarray could become a routine diagnostic tool for CFS. Even more ambitious is the team's effort to integrate this gene expression data with epidemiologic (age, race, sex) and laboratory (blood work, urinalysis) information. "We just recently finished all of the gene expression profiling on a study that was conducted in Wichita, Kan., a two-day clinical study of 250 subjects," Vernon says. "We were able to profile 20,000 genes from 177 subjects, and we are in the process of looking at those gene expression profiles." These Wichita subjects, including people with CFS and healthy people, also underwent a battery of neuroendocrine and immune studies, sleep studies, and tests for cognitive function. "It's actually a very rich and incredibly complex data set," Vernon says. "It's not just two things that we're trying to put together, it's multiple things. For instance your physical symptoms -- quantifying fatigue, levels of cognitive impairment, sleep problems -- with other laboratory measurements, in addition to gene expression measurements." Vernon has assembled four teams of six investigators -- from disciplines including medicine, molecular biology, mathematics, physics and computer science -- to tackle the Wichita clinical data set to try to further the understanding of CFS pathophysiology. "Our group is one of the few multidisciplinary groups there is that's studying CFS. ... I think our group is realizing that it is going to be the way to cure CFS. ... Because of the complexity of this illness, you have to have many different perspectives." How close are we to that diagnostic marker? Vernon pauses. "I hope we're close, is what I would like to say." She laughs. "I don't want to give a date because everybody in my lab will panic." Finding effective treatment for CFS is another long-term goal. "Isn't that the dream of any scientist?" Vernon says. With a better understanding of the disease process, specific therapeutic interventions may one day be possible. But for now, treatment for CFS is limited to managing symptoms, such as pain or sleep problems. However, symptomatic treatments don't address the underlying disease, which, Vernon says, "could end up affecting people for the rest of their lives." What happened to the woman Jessop first saw in her clinic in 1984? "I ran into her about a year ago," says Jessop, who is now an administrator at several East Bay hospitals. "She never enjoyed the life that she had before, but I think she was much better. Certainly she was out of bed and doing things. " Like this woman, the majority of people with CFS gradually improve, but only an estimated 10 percent enjoy full recovery. Many stay the same, and some worsen with time. Questions about who will recover and when remain unanswered." http://www.sfgate.com/cgi-bin/article.cgi?f=/c/a/2005/06/05/CMG3NCLBC81.DTL&type=health 050607 ... skyburst777 "Whistler T, Jones JF, Unger ER, Vernon SD. Exercise responsive genes measured in peripheral blood of women with chronic fatigue syndrome and matched control subjects. BMC Physiology 2005;5:5 The complete electronic version of this article is available at http://www.biomedcentral.com/1472-6793/5/5 Summary Patients with CFS have exacerbated symptoms after physical activity and exercise also induces changes in physiologic function mimicking an infectious or inflammatory state. This study where patients and healthy subjects were challenged with an exercise stress serves is another 'model' system to help us understand the pathophysiology of CFS. Blood samples were drawn before and after exeercise (6 and 24 hours). Microarrays were used to simultaneously assess the expression of 3,800 genes. The patterns of gene expression differed between subjects with CFS and normal controls. The differentially expressed genes have functions related to energy metabolism, muscle response, and immune response. We are continuing laboratory analysis to measure other factors that might help us to better understand these patterns. Abstract Background: Chronic fatigue syndrome (CFS) is defined by debilitating fatigue that is exacerbated by physical or mental exertion. To search for markers of CFS-associated post-exertional fatigue, we measured peripheral blood gene expression profiles of women with CFS and matched controls before and after exercise challenge. Results: Women with CFS and healthy, age-matched, sedentary controls were exercised on a stationary bicycle at 70% of their predicted maximum workload. Blood was obtained before and after the challenge, total RNA was extracted from mononuclear cells, and signal intensity of the labeled cDNA hybridized to a 3800-gene oligonucleotide microarray was measured. We identified differences in gene expression among and between subject groups before and after exercise challenge and evaluated differences in terms of Gene Ontology categories. Exercise-responsive genes differed between CFS patients and controls. These were in genes classified in chromatin and nucleosome assembly, cytoplasmic vesicles, membrane transport, and G protein-coupled receptor ontologies. Differences in ion transport and ion channel activity were evident at baseline and were exaggerated after exercise, as evidenced by greater numbers of differentially expressed genes in these molecular functions. Conclusions: These results highlight the potential use of an exercise challenge combined with microarray gene expression analysis in identifying gene ontologies associated with CFS." http://www.cdc.gov/ncidod/diseases/cfs/publications/causes.htm#24 050607 ... . "CFS strikes people of all ages and ethnic and socioeconomic groups. Most cases in the United States are women between the ages of 40 and 49, but CFS afflicts men, women and children of all ages. In women, CFS is more common than multiple sclerosis, lupus, HIV infection, lung cancer and many other well-known illnesses." 050607 what's it to you? who go blather from