Wednesday, February 6, 2008

Chat w/Dr. Klimas - Part 1 of 3

http://www.immunesupport.com/library/showarticle.cfm?id=8646&T=CFIDS_FM&B1=EM020608F

Q&A Session (held Jan. 11) with Nancy G. Klimas, MD – A Central Figure in International ME/CFS/FM Research and Treatment


ImmuneSupport.com

01-28-2008

Welcome to ProHealth's Live Chat Q&A (held Jan. 11, 2008) with Dr. Nancy Klimas, MD - a noted immunologist and a world leader in ME/CFS/FM/Gulf War Illness research, treatment, education, and advocacy. Dr. Klimas is:

n President of the International Association for CFS/ME (IACFS/ME) –– a global organization dedicated to the exchange of information about CFS/ME and FM research, care, and treatment.

n Professor of Medicine-Psychology, Microbiology, and Immunology at the University of Miami (FL) School of Medicine;

n Director of the University’’s EM Papper Laboratories of Clinical Immunology and VA Gulf War Illness & ME/CFS Research Center.

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Q: Doctor, I have CFS but some people just don't believe I am really ill. I can look so normal and feel so bad. How can I convince them this is real? Is there an online source for research that we can print out to increase awareness about the depths of this debilitating illness?

Dr. Klimas: The CDC has published very convincing studies on this exact question. They have shown that CFS/ME patients can experience a level of disability that’’s equal to that of patients with late-stage AIDS, patients undergoing chemotherapy, and patients with multiple sclerosis. You can find this information on the CDC and the CFIDS Association of America web pages. Here is one meant for doctors: http://www.cfids.org/sparkcfs/health-professionals.asp. The first page of the Physician Toolkit quotes the CDC’’s Dr. William Reeves on this subject. * * * *

Q: Do you feel Chronic Fatigue Syndrome and Fibromyalgia are one and the same?

Dr. Klimas: No, though there is considerable overlap. I don’’t even consider all ME/CFS the same - there are subgroups, and subgrouping is going to be the key to effective therapy. There are already biomarkers in development that will tell both FM and CFS apart and define the overlapping groups - as well as studies to develop the biomarkers that distinguish different subtypes of CFS.

* * * *

Q: Doctor, what do you think of Dr. Jonathan Kerr's gene expression findings? [See ""Seven genomic subtypes of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis"" published in December 2007.]

Dr. Klimas: It is very exciting! His data, and that of Dr. Vernon, should lead to both biomarkers and treatments that are individualized. [Dr. Suzanne Vernon, PhD, was recently named Scientific Director of the CFIDS Association. A research team she led in her previous work at the CDC identified three genetic variations in ME/CFS serotonin synthesis that correlate with different measures of disability and fatigue.]

* * * *

Q: What do you think of the Sakudo diagnostic blood test for CFS using visible and near-infrared spectroscopy? Have you heard any news as to progress on this?

Dr. Klimas: Dr. Sakudo, a researcher at Osaka University, presented additional data at a meeting I attended in Scotland last summer –– the International Conference on ME/CFS Biomedical Research. It’’s still looking good.

* * * *

Q: Any thoughts on Dr. John Chia’’s findings on enterovirus in stomach biopsies, published last fall? [An enterovirus is defined as ""a virus that enters the body through the gastrointestinal tract and thrives there, often moving on to attack the nervous system.""]

Dr. Klimas: Isn’’t that interesting! Dr. John Gow at the University of Glasgow had some early data suggesting enterovirus in the muscle, but it didn’’t really pan out. Now we have this important study on the gut! Shows how important it is to look in every type of tissue.

The main thing here is to remember that when the immune system lets one virus out, it can let out many –– and antivirals directed at HHV-6 (Human Herpesvirus 6) and EBV (Epstein-Barr virus) aren’’t going to work on enterovirus. Of course, I am an immunologist and believe immune boosting drugs may be very important.

* * * *

Q: Dr. Klimas, do you know much about Dr. Gow’’s recent research? It seemed to be showing promise a few years ago, but I have heard nothing recently.

Dr. Klimas: Last time I spoke with Dr. Gow, he was working on a genomics project, and had some pretty cool data. I haven't heard him talking about enterovirus for a while.

* * * *

Q: Is your hunch that this is a viral and/or bacterial illness (or illnesses) that is still active in patients, or do you think that it is a "hit and run" attack on the brain?

Dr. Klimas: Oh, both I think. It’’s all back to subgroups with this question. I know that there are patients with reactivation viruses active right now (look to Dr. Dan Peterson, Dr. Martin Lerner, and Dr. Jose Montoya for their work in HHV-6 and EBV infection). And enterovirus reactivation is a worry (see Dr. Chia’’s study on this subject). That does not mean these pathogens started the process - but that they help maintain it.

* * * *

Q: I have been ill since I had mono 10 years ago. Why am I still sick when others recover completely from mono?

Dr. Klimas: A recent prospective study found that the one single predictor of who is going to stay sick after a viral infection is the severity of the initial viral infection. Patient advocates have been happy to note that there were no psychiatric predictors.

I suspect that the most important factors are a combination of genetics, immune function at the time of the inciting infection, and the inciting virus itself. The virus that causes mononucleosis (Epstein-Barr virus –– EBV) is particularly tough on the immune system.

* * * *

Q: My chronic fatigue illness started with infectious mono. After about a year, a very low vitamin D level was discovered. My doc thinks that this played a role in my immune system failing to contain EBV. Are there any references on this?

Dr. Klimas: Low vitamin D is a frequent finding even in my sunshine state –– Florida - and vitamin D is important to immune health. But I don't now if it was there to begin with or is a consequence of the illness.

* * * *

Q: Is it possible to have recurring bouts of EBV?

Dr. Klimas: There have been studies that show viruses at high levels during relapse and low during relative good times - mostly HHV-6 though. (Konnie Knox, PhD, at the Wisconsin Viral Research Group, did this work.)

* * * *

Q: The glands under my ears are often tender and sometimes visibly swell up. What could be causing this?

Dr. Klimas: There are lymph nodes there and your parotid glands, which help make saliva. Epstein-Barr virus loves to hang out in parotids...

* * * *

Q: Are you optimistic with regard to Dr. Montoya's work with the antiviral drug ValcyteTM [generic name valganciclovir] - its ability to help a subset of ME/CFS patients with chronic HHV-6 and EBV infection? And if so, do you agree that a positive correlation in his study, if found, will go a long way in legitimizing this illness?

Dr. Klimas: The first research to achieve an FDA label on any drug will go a long way to legitimize this illness –– look at LyricaR and FM! [Lyrica was the first prescription drug to receive FDA approval.] But it would be gratifying if that first label were on an antiviral or immunomodulator.

* * * *

Q: When will the results of Montoya’’s phase 2 trial of valganciclovir be published?

Dr. Klimas: I am hoping they will finish the data collection part of the study by June 2008 - but analysis and publication take time!

* * * *

Q: Treatments you are currently using or see possibly being helpful in the near future? How soon?

Dr. Klimas: 1. I am still hopeful that the IsoprinosineR company, Newport Pharmaceuticals, will move on the Phase 3 trials. [Results of the Phase 2 trial in Canada were summarized in the 2003 article ""Clinical Improvement in Chronic Fatigue Syndrome is Associated with Enhanced Natural Killer Cell-Mediated Cytotoxicity"".]

2. AmpligenR is at the FDA asking for a label. [Ampligen is believed to support upregulation of the immune system’’s RNase-L response to viral infection.]

3. By subgrouping, ME/CFS patients with elevated cytokine TNF-a may be directed to protocols using TNF inhibitors or blockers. [TNF –– tumor necrosis factor –– promotes inflammatory response. Jonathan Kerr, MD, PhD, director of a large ME/CFS human and viral gene expression study in the UK, announced at the 2007 IACFS/ME conference that he was engaged in a trial of the TNF-a inhibitor, Etanercept (EnbrelR), in a select number of CFS patients.]

* * * *

Q: Is there any test that you consider promising to diagnose ME/CFS?

Dr. Klimas: Yep - the exercise physiology group at the University of the Pacific Fatigue Lab presented data at the IACFS/ME conference on next-day decreases in exercise capacity after an exercise stress test. It’’s a great model, and we are taking advantage of it! [The report, just published, is "Diminished Cardiopulmonary Capacity During Post-Exertional Malaise." A companion study - "Legal and Scientific Considerations of the Exercise Stress Test" - analyzes the test's potential use for disablity insurance purposes.]

* * * *

Q: What is your impression of the drug LyricaR for Fibro treatment? Or any other meds you recommend?

Dr. Klimas: I like Lyrica, or sometimes gabapentin - which is a lot cheaper - for pain management, which in turn can help sleep. [Gabapentin –– brand name Neurontin - no longer has patent protection so is available as a generic.] I always start with sleep management, as restorative sleep is key to any improvement. There is a Fibromyalgia study underway using a stage 4 sleep inducer, Xyrem, which I believe is very promising.

* * * *

Q: Thoughts on low growth hormone in CFS?

Dr. Klimas: This is an important observation, though it could result from poor quality stage 4 sleep. I would not consider a treatment plan using growth hormone unless sleep has been addressed and the growth hormone was so low that it met criteria for Adult Growth Hormone Deficiency.

* * * *

Q: Doctor, can you give us your best sleep remedy?

Dr. Klimas: Magic pills...everyone wants a magic pill. It’’s just not that easy. But sleep can be worsened by many sleep remedies - particularly valium-like drugs such as RestorilR (generic name temazepam). Some of the newer drugs hit these same receptors - like LunestaR.

I think if you wake up exhausted you need a sleep study in a sleep lab - first to rule out things like apnea, but also to document the need for stage 3 and 4 sleep. Then treatments exist to address these problems.

* * * *

Q: Why would my fatigue come and go? It is not related to my sleep. I sleep very well every night.

Dr. Klimas: It is the nature of this illness to have good days and bad, and they are not always related to the quality of sleep. We have a study going on at our research center which we call the "Good Day/Bad Day"" study, trying to figure this out.

* * * *

Q: I dream every night and when I wake up I'm so tried. Am I getting good sleep?

Dr. Klimas: Get your doctor to refer you to a good sleep expert - I often suggest a neurologist, as they are thinking about central (brain) causes for sleep problems. Though the key is to have a doctor who is willing to manage and not just diagnose.

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