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SBM: Kogelnik, Rituximab and CFS: Jumping the gun

Discussion in 'General ME/CFS News' started by Firestormm, Jan 13, 2013.

  1. barbc56

    barbc56 Senior Member

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    Purple

    Oops, thanks!! That should be OMI or the Open Medicine Institute where Dr. Kogelnik works. I will go back and change this and then the others when I have the time. You know how it can be so exhausting writing a post.
    Thanks.
  2. Purple

    Purple Bundle of purpliness

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    It's Dr Kogelnik and Dr Mella and Dr Fluge - it would be good (and respectful to everyone involved) to get the names of the people talked about right.
  3. barbc56

    barbc56 Senior Member

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    LOL!! Talk about fog. The names I used were ones I saved in my spell check. I think I do remember how to spell my own name. At least most of the time.:D
    Barb
  4. Ecoclimber

    Ecoclimber Senior Member

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    This is not a two-bit operation! Open Medicine Institute has some very heavy 'hitters' on board unlike some other research centers to remain 'nameless'. Dr. Kogelnilk has an impeccable background with both a MD and a PhD! His organizational staff - management, board and advisors - is very impressive! Perhaps many are unaware of his background.

    Dr. Andreas M. Kogelnik, is the Founding Director of the Open Medicine Institute, a collaborative, community-based translational research institute dedicated to personalized medicine with a human touch while using the latest advances in medicine, informatics, genomics, and biotechnology.

    The Institute works closely with the Open Medicine Clinic and other clinics to conduct research and apply new knowledge back into clinical practice.

    Dr. Kogelnik received his M.D. from Emory University School of Medicine in Atlanta and his Ph.D. in bioengineering/bioinformatics from the Georgia Institute of Technology. Subsequently, he completed is residency in Internal Medicine and a Fellowship in Infectious Diseases at Stanford University and its affiliated hospitals.

    Following his clinical training, he remained at Stanford with NIH funding to engage in post-doctoral research in microbiology, immunology and bioinformatics with Dr. Ellen Jo Baron and Dr. Stanley Falkow, where he explored host-response profiles in severely ill patients.

    Together with Dr. José Montoya, he was instrumental in the conception, design, and execution of the EVOLVE study - a placebo-controlled, double-blind study of a subset of chronic fatigue syndrome patients with evidence of viral infection.

    Dr. Kogelnik worked with Dr. Atul Butte in translational informatics to determine patterns that indicated a high risk for adverse events in paediatric patients at Lucille Packard Children's Hospital.

    He is the Medical Director of the Open Medicine Clinic - a community-based research clinic focussed on chronic infectious diseases, neuroimmune disease, and immunology. Dr. Kogelnik has published numerous scientific papers and book chapters, is an Editor of Computers in Medicine and Biology, and is a Consulting Assistant Professor at Stanford University.

    With the Open Medicine Institute, he has led the formation of CFS and Lyme Registries and Biobanks as well as creating an infrastructure for providers to collect better data and implement clinical trials across a network of sites.

    Advisors:

    Thomas Fogarty, MD is an internationally recognized cardiovascular surgeon, inventor, entrepreneur, and vintner. Dr. Fogarty has served as Founder/Co-founder and Chairman/Board member of over 33 various business and research companies, based on devices designed and developed by Fogarty Engineering, Inc. During the past 40 years, he has acquired over 100 surgical patents, including the “industry standard” Fogarty balloon embolectomy catheter. Dr. Fogarty is the recipient of countless awards and honors.

    Vinod Khosla is a highly successful venture capitalist, having founded, led, and funded many of the high-tech and biotech companies that have shaped our world. In the early 1980s he was a co-founder of Sun Microsystems where he served as its first CEO and Chairman. In 1986, he became a general partner of the venture firm Kleiner, Perkins, Caufield & Byers where he remained through the early 2000s. In 2004 Khosla formed his own firm, Khosla Ventures, which focused on investments in various technology sectors, most notably clean energy. He gained a Bachelor of Technology in Electrical Engineering from IIT Delhi, a Masters in Biomedical Engineering from Carnegie Mellon, and an MBA from Stanford.

    Jay Levy, MD is a leading virology and cancer research as a Professor of Medicine at the University of California San Francisco where in 1983, he co-discovered the HIV virus. Dr. Levy has published over 450 scientific articles and has authored and edited 14 books dealing with viruses and immunology. The San Francisco Examiner chose him as one of the ten most influential people in the San Francisco Bay Area.

    Randy Scott, PhD has been at the forefront of genomics and personalized medicine for over a decade. He was the founding president and CSO at Incyte and recently was the founder and CEO of Genomic Health where he led a team to develop the first commercial genomic-based clinical diagnostic, OncotypeDx. Dr. Scott is now focusing on a new commercial start-up venture, Invitae.


    Board:
    Chris Burggraeve is a leading global marketer and entrepreneur. Over the last 23 years, he has built world-class marketing capabilities in developed, developing, and emerging markets. After initial experience in technology startups, he worked in brand management and general management for Procter & Gamble, the Coca-Cola Company,

    Ron Davis, PhD is a Professor of Biochemistry & Genetics and Director of the Stanford Genome Technology Center. Dr. Davis, with David Botstein, Mark Skolnick, and Ray White developed the method for constructing a genetic linkage map using restriction fragment length polymorphisms that led to the Human Genome Project.

    Allan May is a Director at Emergent Medical Partners and has been a Founder, Board member and/or CEO of multiple successful biotech and device start ups including AngstroVision, Athenagen, IntegriGen, NuGen Technologies, and Vascular Architects. He has held senior executive roles at two publicly-traded companies. In 2005, he co-founded the largest angel investment organization in the US—Life Science Angels—and currently serves as its Chair.

    Management:
    Ray Teeling is Director of Outreach and has been involved in software sales and managed services in the telecommunications and information technology industries for over 15 years. Mr. Teeling is adept at opening new markets, growing a customer base, and building revenues for high technology integration services organizations and Global 1000 and Fortune 50 customers in the US.

    Kenneth Ng is Director of Mobile Technologies and has spearheaded the development of successful applications on multiple mobile device platforms and other integrated tools for the past five years. He has over 15 years of experience in information technology and engineering. With Dr. Kogelnik, he has developed numerous prize winning mobile health apps for the Robert Wood Johnson Foundation, Health 2.0, and Office of the National Coordinator for Health IT (Dept. of HHS, US Govt).]

    Jennifer Larson is Director of Communications. She joined OMI from DermTech, where she led Business Development for the company’s genomic assays. Her background includes managing employee relations and EU media activities at Novartis; directing public relations teams at Porter Novelli London for clients including Novartis, Pfizer, and Boston Scientific; investor relations and corporate communications at Chiron; and sales at Bristol Myers-Squibb. She is a partner at Labfive, a consulting group. She received her BA from Berkeley and did graduate studies in molecular biology at Berkeley and the University of Sydney.

    Eco
    alex3619 likes this.
  5. barbc56

    barbc56 Senior Member

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    I think the Institute certainly sounds promising and maybe what Kogelnik is doing is not unethical in the strict sense of the word. But I just feel it's too soon, especially taking into consideration what Mella and Fluge have stated. Obviously, other's disagree and that's all right. It's just my personal opinion that there's a possibility things are going too quickly before all the information is sorted. I think we can all agree to disagree on this. I keep my fingers crossed that the Rituximab studies will be a promising start on the road to helping us. We could certainly use a break. A huge break!!! No, a ginormous break as my granddaughter would say. :)

    Barb
  6. Valentijn

    Valentijn Activity Level: 3

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    At the end of the day, do we really care if B cells are the cause or effect, if a treatment for B cells removes a very nasty symptom that nothing else even really touches?
    I think most expectations regarding Rituximab are realistic. It might work, it might not. It might work for a while, or it might just work a little. Or it might make us worse. But thus far there are indications that it does work to some extent, that harm is very unlikely, and there is a somewhat sensible outline of an explanation for why and how it might work. CBT and GET on the other hand, are shown not to work, are widely claimed to cause harm, and make no sense in the context of treating ME/CFS.
    All ME/CFS patients are not the same. Some are strongly anti-vaccination, and some are undoubtedly very eager to try Rituximab. There is no evidence that these two groups overlap. Furthermore, you're talking about very different treatments with very different effects and potential side-effects.

    Flu vaccinations require a healthy immune system, which evidence suggests we do not have. A lot of us don't get out much so aren't exposed to much. Some of us became ill after vaccination. The consequences of not being vaccinated are relatively mild. There are nasty substances in vaccines which the body needs to detox, an area in which we might be impaired. There have been studies specifically of CFS patients following vaccination, and there was an abnormal immune response. In the case of ME/CFS, there is plenty of reason to believe that the potential benefits of flu vaccination do not outweigh the potential risks.
    Do you have a link to support this statement?
    I'm glad we're all in agreement then.
    penny likes this.
  7. barbc56

    barbc56 Senior Member

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    This is not the quote I was looking for but it basically says the same thing, just not as emphatic. Remember this is translated. I have also written someone in Norway who may provide me with the quote.
    http://www.tv2.no/nyheter/innenriks/helse/-naar-kan-vi-andre-faa-mebehandlingen-3615662.html
  8. barbc56

    barbc56 Senior Member

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    I would hope this very important question would be looked at by researchers.
    So again I would have to ask why take something where we don't know the benefits vs.risk profile.
  9. Firestormm

    Firestormm Senior Member

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    The OMI is not an issue raised by the OP. Kogelnik and his presumed (by his patient) 'pilot study' that wasn't - was. The 'jumping the gun' raised an important debate about whether or not it is 'right' (by way of debate and not legal judegment) for ANY doctor to be prescribing Rituximab BEFORE it has been as definitively as science allows - is shown to be of benefit for people with ME.

    There is a lot we do NOT know about Rituximab and what it does or doesn't do for people with ME. If people with ME have a 'weakened' immune system to the extent that some are snubbing vaccination - then WHY take a drug that will destroy your B-cells. Cells that are VITAL for immune system defence? Makes no sense to me whatsoever.

    We also know that for some people a subsequent 'virus' can last a long time and/or lead to a relapse. So again I ask why risk Rituximab and destroying B-Cells. This is not like eating smarties.

    This needs more research. Fluge and Mella have no idea why Rituximab appears to have worked in their study. They didn't BLIND* their study. They do not appear to have taken the same degree of care with subsequent pilots in terms of blinding and controls as they did with the initial study as these are 'open trials'; and that initial study was critiqued for the end-point-measures of improvement (see OP for example).

    They are however, willing to continue to find some answers and hopefully subsequent research will contain more patients, similar blinding and controls and more objective/appropriate endpoints i.e. will address the critiques that their first study did. And the same should hold true for OMI studies and studies from anyone else for that matter. Let's see the science move forwards.

    Additional work with B-cells/Immunity and ME needs to be done. A LOT more research. We have been hearing and seeing studies for ages that appear to indicate we have a 'dysfunctional' immune system - but nobody knows why. How can this be the same for everybody - or even for some - and to what extent - when we are all entering ME by different routes?

    How can this be explained by somebody who - presumably and by their own anecdotal stories - are here in this 'pot' because of a 'bad reaction' to a vaccine when at the same time others (like me) are here because of a virus? Or similarly, those who feel strongly that they are here because of 'mould toxins'?

    If Fluge and Mella were assessing their entrants to a study based upon, for example, the extent to which their B-cells were damaged as in Rheumatoid Arthritis, then we might have a case for treatment. But they haven't. And neither - to our knowledge - has Kogelnik.

    This is yet another example of a doctor experimenting on his patients. As with Ampligen. As with Anti-retrovirals. It might be perfectly within his remit to do so. It might indeed be 'ethical'. I really couldn't say. But it wouldn't happen in the UK by an NHS Doctor without the necessary research and approval.

    If Kogelnik was performing a clinical trial or a 'pilot study' it should - apparently - have been registered. It wasn't. His patient made a mistake allegedly. I very much look forward to Kogelnik registering a proper clinical trial and carrying this out properly as part of an OMI initiative. This is in my view the ONLY way we will proceed positively with Rituximab (or it's newer clones).

    As a Brit I do not personally agree with any doctor charging patients or advertising (not that Kogelnik has although patients got to him somehow) for treatment with a drug that has not been shown to work. Rituximab is in my view experimental and potentially dangerous - see previous blog about MS and the concerns raised.

    We are again facing a dilemma here. Patients are desperate and want it - MS included - and the advice is not to take it and wait for more research. If you have to money then the very best of luck. I'd like to know how this doctor assesses his patients as being likely to benefit from it and how he monitors progress and how he concludes treatment has been effective. If the latter relies solely on a patient saying or demonstrating 'I feel better' then it isn't good enough for me I am afraid.

    (*Either that or they didn't use controls I can't recall offhand)
    Post edited. Thanks Purple.
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  10. Valentijn

    Valentijn Activity Level: 3

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    That's not just less emphatic, it's a completely different message. If anything, they're saying patient experience outside of trials is helpful, and it's "unfortunate" that most patients (have to?) wait.
    penny likes this.
  11. Valentijn

    Valentijn Activity Level: 3

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    We do know in the case of Rituximab, to some extent. The drug has been used extensively for other conditions, which has established it as being pretty safe. The drug has been used in small randomized blinded ME/CFS trials, which shows pretty impressive benefits.

    If science waited until there were multiple trials involving thousands of patients with 0 risk and 100% permanent efficacy, there'd be no treatments for any condition. Yet that seems to be the threshold you and others continue to demand for ME/CFS use of certain drugs or even supplements!

    Stop playing on "risks" already. YES it is a drug used for cancer treatment. That does NOT automatically make it particularly dangerous. It makes it highly tested and with a very good safety record. I can read the research and have done, and the fear-mongering is getting really old.
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  12. Purple

    Purple Bundle of purpliness

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    Mella and Fluge's study with 30 subjects was both blinded and controlled. As you are a prolific debater on this site, you should clarify for yourself what these terms mean so as not to mislead readers.
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  13. Firestormm

    Firestormm Senior Member

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    Fair enough. When I get a moment to read the paper again I shall. Or you could have clarified the matter also. Doesn't change any of my thoughts on the issue. Or Mella and Fluge's desire to hold more thorough studies either.
  14. Firestormm

    Firestormm Senior Member

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    Post duly edited :)
  15. barbc56

    barbc56 Senior Member

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    The following is quite interesting. It's a letter to the editor of PLOS ONE, critiquing the Mella/Fluge study. In the following quote, Fluge is responding to concerns that physicians might be prescribing Rituximab on their own and in a non research setting.
    (My bold.)
    http://www.plosone.org/annotation/listThread.action?root=6147
    I would highly recommend reading the complete article.
    Barb
  16. In Vitro Infidelium

    In Vitro Infidelium Guest

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    That is to mix contexts in ways that produce nothing more than - "please stop making your point, I don't like it". None of the conversations on an internet forum are fixed - people are coming and going all the time, and unless there is definitive material to direct people to, then new readers may well be interested to see that some people are sceptical, or concerned or have a different perspective than those who are enthusiastic about (other people ?) experimenting with off label or non medical treatments.

    All medical interventions have risks and the usefulness of a particular intervention is dependent upon resultant harm being outweighed by resultant benefits. Benefits and harms vary from condition to condition, and from individual to individual. Just because because a treatment has proved 'safe' in cancer treatment, can't possibly be a basis for assessing safety in conditions where fundamentally different biological processes are in play. Personally I'm doubtful about the role of persistent infection in M.E/CFS but it certainly can not be ruled out as being a significant factor in M.E/CFS aetiology(ies). For anyone who considers persistent and variably occult infection to play a role in their ill health, it seems only logical that depleting part of the immune system may have adverse consequences - that ought be something that is frequently repeated in circumstnces where concern for the health of others is considered important.

    While it would sem improbable that anyone with M.E/CFS symptoms should not have been screened for Hepatitis B, we know that M.E/CFS is a misdiagnosis given to patints who have other serious illnesses - on that basis alone it is reasonable to keep in mind that rituximab therapy is not without dangers - as I posted previously: Fatal hepatitis B virus reactivation by an escape mutant following rituximab therapy . Of course it's to be hoped that Kogelnik and any other physician offering rituximab to M.E/CFS is ensuring exclusion of Hep B as a matter of course, but in the absence of published protocols it seems appropriate to comment when the issue of 'safety' arises.

    And this isn't just about the safety of thse being treated - any serious incident with a treatment can have the effect of disuading researchers to take an interest. As I've argued previously, the importance of rituximab for M.E/CFS is not as a viable widely available treatment, but as tool for investigating in vivo disease processes in M.E/CFs sufferers. Major diasbility or deathrsulting from treatment of M.E/CFS patients with rituximab could destroy any use the drug may have in definitive M.E/CFS research. That is a matter of concern to all of us - I don't see why those of us who have that concern should be expected not to raise it.

    IVI
  17. CallieAndToby

    CallieAndToby Senior Member

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    I think we assume that a very expensive CFS doctor is going to cover other things in addition to M.E./CFS (she knew about his main approach), that's what I thought when I went to miami. Also, she's mostly bedridden and he was nearby, not all patients are well enough to do research. I.E. I have seen a CFS doc who tried to treat any sleep issues as well as did tilt table tests, tested for lyme, etc. etc.
  18. JayS

    JayS

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    Which doctor or doctors experimented on patients with Ampligen outside of clinical trials?
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  19. Firestormm

    Firestormm Senior Member

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    Ampligen is not approved. It is an experimental and new drug. It was marketed as being beneficial for such diverse conditions as HIV treatment. Any doctor prescribing the drug was experimenting. Again. It may not be 'wrong' or illegal but it is experimental.

    Not all the people on this post from Cort by way of example, were claimed to have been part of a clinical trial. Several were said to have been taking Ampligen for over 10 years. Maybe they were all part of a trial - but it doesn't read like that.

    If every person who has ever taken Ampligen that I have read accounts of on the internet over the years was in a trial I would expect them to say so. If I am wrong I am wrong.

    But Ampligen is experimental until proven otherwise by regulatory approval which would require better science that has occurred to date.

    To my mind, and as I have said before on this thread, several of my own drugs are 'off label'. But they are approved and recognised drugs for symptoms that are recognised as affecting me personally. They are not for ME specifically.

    Ampligen and Rituximab are being argued as appropriate for ME. I have asked previously how these doctors assess a patients suitability for either drug, and I have yet to hear. I have asked how these non-approved drugs are monitored and how risk is assessed. Not to judge but to try and understand.

    I want proper clinical trials to proceed. More so with Rituximab. I want the critiques to be answered with solid science. My money has always been on the immune system.

    I don't understand how/in what way Rituximab can have the kind of effect it was promoted as having. Neither for that matter do I with Ampligen and the results with that drug - in trial - were less impressive to me.

    I would like to try and better understand.
  20. Firestormm

    Firestormm Senior Member

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    This old post from 2011 talked about a potential open-label trial for Ampligen. Whilst charging fees - which is the norm I understand in the USA - it did talk about "extensive testing to determine eligibility" and "procedure expenses (infusion costs, bloodwork, X rays, EKGs and other testing)".

    It was to have been conducted by Bateman. My point would be that I'd like to hear more about what tests for eligibility Kogelnik undertakes and for monitoring and for showing that Rituximab has worked (or indeed not worked). Similarly for Bateman – assuming the above trial proceeded.

    This might be how people were receiving Ampligen and are receiving Rituximab i.e. through 'open-label' trials. But those trials or any ‘pilot studies’ apparently need to be registered. And apparently Kogelnik hasn't registered any - according to Dr Hall in the OP.

    Have doctors been prescribing Ampligen outside of any trial? I don’t know. Not without asking each and every one patient who has posted of their experience. Have they benefitted from taking Ampligen – apparently some of them have: very much so. Some have not.

    What relevance their improvements have to regulatory approval for Ampligen or indeed Rituximab compared to a properly conducted, significant, blinded and controlled clinical trial (that doesn’t charge patients for the privilege); and which demonstrates efficacy and safety as well as improved health…. Well from my perspective I would suggest that open-label trials are mere shadows.

    They must have their uses however but I don’t know what they might be. Funding may play a part i.e. it must surely be cheaper to have patients paying for the treatments and monitoring in an open-label trial that otherwise.

    Does open-label come before a full clinical trial? Are open-label trials unique to the USA? Or only in regard to charging patients or experimental treatments? I don’t know. Never really looked into it before.

    In what way do open-label trials contribute to the scientific knowledge? Again I don't really know. Do they result in published papers - has Kogelnik published a paper? I don't believe he has but I'd like to read more about his thoughts on Rituximab and why and in what way he is prescribing it now.

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