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Dr. Judy Mikovits IACFS/ME Newsletter Apr 2010 Q & A

Discussion in 'XMRV Research and Replication Studies' started by shrewsbury, Apr 21, 2010.

  1. usedtobeperkytina

    usedtobeperkytina Senior Member

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    I have

    I have another news reporter interested in an XMRV / CFS story. This would be the largest circulation newspaper in the state. I would love to send a link to this, but it is not presentable. But I summarized the parts in this that are new, that is not previously known. Someone commended me for summing things up before. So here is my version of this. (Please understand, if it is old news or I don't understand it, it is not included)

    • The virus infects Natural Killer cells. Yet Natural Killer cells also kill other cells that are infected with the virus. Mikovits experimented with a medicine that increases the ability of Natural Killer cells to kill other diseased cells. This is in response to a question as to whether neutraceuticals for increasing replication of Natural Killer cells would be advisable as a treatment for those who have XMRV, if it would increase XMRV replication because it lives in those cells.
    • Based on the type of retrovirus XMRV is, it is likely more transmissible between people as compared to HIV. They have found the virus in the saliva and prostate secretions. Based on evidence seen, Mikovits' theory is that it is the most stable human retrovirus to date. But no retroviruses are transmitted through the air. If the hypothesis is found to be true, then this would explain the fact that CFS often occurs in "outbreaks" or "clusters" and also occurs sporadically.
    • MS drugs to calm the immune system may help to prevent XMRV from spreading or replicating in infected person.
    • XMRV is a C-type retrovirus, which in animals can cause disease in brain without causing the immune system dysfunction. This brings up the question if XMRV could be causing CFS in some individuals and other neurological diseases in others who don't have CFS.
    • "I am extremely optimistic that treatment of XMRV or its immune targets will restore at least 85% of the original health status even in the sickest of the sick," said Mikovits. She is basing that on the lesser impact XMRV has on immune system and the success seen in HIV treatment. But, concerning HIV, she said, "...its (XMRV) effects on the immune system are more subtle." (my note- this would explain why we don't die but just have chronic illness with good days and bad days.)
    • The only immune system abnormality that shows up in 100% of people with XMRV is decrease in interferon alpha.
    • XMRV is gammaretrovirus which can be transmitted through breast milk. Studies suggest that lactating moms express more XMRV in breast milk.
    • Mikovits is finding some are culture positive for XMRV but antibody negative. This suggests that immune therapy including antibody therapy may be helpful in the disease.
    • They are finding some with Lyme disease also have XMRV. The theory is that Lyme is a co-infection.
    • It is important to stop replication of XMRV early after infection, so it doesn't get into longer-living cells where it may be altering the gene expressions of that cell. Since the cell is long-living, it isn't replaced by healthy ones. Once in that cell's DNA, the damage is done.

    Tina
     
  2. natasa778

    natasa778 Senior Member

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    Increased in brain and spinal fluid. no data on blood levels, that I am aware of.
     
  3. Gerwyn

    Gerwyn Guest

    XMRV shows a preference for integrating within the start codons of certain genes.It can act as a pseudogene sometimes called a gene switch.If it gets into some genes the effects might not ne noticeable or lead to very mild vauge unwellness.

    If it integrates within a gene which reguales other genes then we have all the ingredients for a party

    One such example is the gene complex that regulates the immunesystem by kicking off the innate or inflammatory response called TFNalpha.This is the gene that interferon alpha binds to.

    The real doozy however is that XMRV integrates into the creb gene regulating what is called the CREB/CRE system

    The CREB gene is responsible for the protection of nerve cells maintaining plasticity and preventing the natural tendancy towards neuron death.

    The CREB /CRE system contolls gene expression allo ver the body including those that ensure mitochondrial function directly and indirectly.

    As a nice little twist mitochondrial mutations however small and on their own ,may produce someone prone to infection for example.will magnify any abnormaity in the CREB/system.Mitochondrial mutations and creb transcrirtional abnormalities can interact turning the party into a full scale riot

    Creb CRE produce proteins which control the binding of interferon alpha to the TFN alphs gene blocking this binding will have a serious effect on.It is possible to block interferon binding of alpha but enhamce B producing the innate responses observed in patients with ME and of course lead to a higher level of free interferon alpha that Judy M was talking about

    So its just not getting the XMRV but how it interacts with essential gene systems or not that determines having symptoms the severity of those symptoms and the spread of bodily systems dysregulated.

    CREB proteins also control the expression of enzymes essential for the function of the methylation sysytem dysfunction would lead to at leat a partial block--The key one is methionine synthase

    For the GEEKS there is the following information

    he protein kinase A (PKA) and the cAMP response element (CRE) binding protein (CREB) signaling pathways mediate plasticity and prosurvival responses in neurons through their ability to regulate gene expression. The PKA-CREB signaling mechanism has been well characterized in terms of nuclear gene expression. We show that the PKA catalytic and regulatory subunits and CREB are localized to the mitochondrial matrix of neurons. Mitochondrial CRE sites were identified by using both serial analyses of chromatin occupancy and chromatin immunoprecipitation. Deferoxamine (DFO), an antioxidant and iron chelator known to inhibit oxidative stress-induced death, activated mitochondrial PKA and increased mitochondrial CREB phosphorylation (Ser-133). DFO increased CREB binding to CRE in the mitochondrial D-loop DNA and D-loop CRE-driven luciferase activity. In contrast, KT5720, a specific inhibitor of PKA, reduced DFO-mediated neuronal survival against oxidative stress induced by glutathione depletion. Neuronal survival by DFO may be, in part, mediated by the mitochondrial PKA-dependent pathway. These results suggest that the regulation of mitochondrial function via the mitochondrial PKA and CREB pathways may underlie some of the salutary effects of DFO in neurons.

    Mitochondrial Cyclic AMP Response Element-binding Protein (CREB) Mediates Mitochondrial Gene Expression and Neuronal Survival*

    1. Junghee Lee‡,
    2. Chun-Hyung Kim,
    3. David K. Simon∥,
    4. Lyaylya R. Aminova∥,
    5. Alexander Y. Andreyev**,
    6. Yulia E. Kushnareva**,
    7. Anne N. Murphy**,
    8. Bonnie E. Lonze‡‡,
    9. Kwang-Soo Kim,
    10. David D. Ginty‡‡,
    11. Robert J. Ferrante‡,1,
    12. Hoon Ryu‡,1,2 and
    13. Rajiv R. Ratan

    + Author Affiliations

    1.
    ‡Neurology, Pathology, and Psychiatry Departments, Boston University School of Medicine, Boston, Massachusetts 02118, the Geriatric Research Education and Clinical Center, Bedford Veterans Affairs Medical Center, Bedford, Massachusetts 01730, the Molecular Neurobiology Laboratory, McLean Hospital and ∥Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, **Mitochondrial Biology, MitoKor, San Diego, California 92121, the ‡‡Department of Neuroscience and Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, and the Department of Neurology, Weill Medical College of Cornell University and Burke-Cornell Medical Research Institute, White Plains, New York 10605

    1. 2 To whom correspondence should be addressed: GRECC 18B, Bedford Veterans Affairs Medical Center, 200 Springs Rd., Bedford, MA 01730. Tel.: 781-687-2922; Fax: 781-687-3515; E-mail: hoonryu@bu.edu.


    Next Section
    Abstract

    Cyclic AMP response element-binding protein (CREB) is a widely expressed transcription factor whose role in neuronal protection is now well established. Here we report that CREB is present in the mitochondrial matrix of neurons and that it binds directly to cyclic AMP response elements (CREs) found within the mitochondrial genome. Disruption of CREB activity in the mitochondria decreases the expression of a subset of mitochondrial genes, including the ND5 subunit of complex I, down-regulates complex I-dependent mitochondrial respiration, and increases susceptibility to 3-nitropropionic acid, a mitochondrial toxin that induces a clinical and pathological phenotype similar to Huntington disease. These results demonstrate that regulation of mitochondrial gene expression by mitochondrial CREB, in part, underlies the protective effects of CREB and raise the possibility that decreased mitochondrial CREB activity contributes to the mitochondrial dysfunction and neuronal loss associated with neurodegenerative disorders.
     
  4. bel canto

    bel canto Senior Member

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    Wow! So xmrv may be partying in some and rioting in others. And, presumably, just hanging out in the the luckier ones.

    Thanks once again, Gerwyn, for your help in translating all this into lay terms.
     
  5. lansbergen

    lansbergen Senior Member

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    I think you have got that right.
     
  6. JAS

    JAS

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    Is it just me or is this frightening the life out of everyone too.

    For Sale: 1 Retrovirus, 1 careful lady owner, Full service history, Private Insurance, Reasonable Mileage. Extras: spoiler, Cruise Control, Central Locking, Immobiliser, De-conditioning, Climate control (faulty) Private Reg XMRV. Free upgrade for ME available. Any offer accepted.

    (Thanks to Fingers for the De-conditioning bit!)
     
  7. coxy

    coxy Senior Member

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    i'm really pleased to see Dr chia showing such interest in XMRV. I think he's done some great work with the gut issues & by the comments from Dr M it looks like there could easily be a link there, showing both doctors to be going down the correct route to finding a cause.
     
  8. Overstressed

    Overstressed Senior Member

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    I'm wondering if somebody had a thought about this:

    - if XMRV turns out to be the cause of CFS and other diseases
    - and if it is so stable, it can be transmitted easily through body fluids (e.g.saliva)

    what might happen to us then ? Will we be excluded from society ? My wife is a teacher, and seems to be infected too, will she be allowed to carry out her job ? If not, the disease will not kill her, but, excluding her to teach children will kill her. Teaching is her life.

    I think, we will be excluded from society, people will avoid shaking hands etc... Look at what happens when people turn out to be HIV+ by means of ignorance ? I get a very bad feeling about this...

    Take care,
    OS.
     
  9. pollycbr125

    pollycbr125 Senior Member

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    i worked in education with severley disabled children i have no doubt in my mind that ,that is how i became ill . i was bitten by a child and severley ill within days . so if i am xmrv pos i have no doubt that mine would have been transmitted by saliva . however proving it is another matter . the child who bit me had severley delayed development . he was ill at the time possibly a throat infection infact we were waiting for mum to pick him up . like many of the kids i worked with he was one of the ones with an undiagnosed syndrome but he would definately fit on the autistic spectrum somewhere .so in my case a lot of this would make sense .

    the prevelance of teachers and educational teaching assistants becoming ill with me/cfs is quite staggering i think its the second highest prevelance below people who work in medical establishments .but when you think about it these place are the perfect enviroment for bugs to be rife .

    if i am xmrv pos i have no doubt that if i were to become well again i would not be allowed back into teaching . i miss it with a passion so i can empathise with your wife OS . being stuck between a rock and a hard place springs to mind . but then if i think at the other side of the coin would i want to go back to a job which inadvertantly made me ill ?

    ill be honest i havent a clue what i will do if i become well again , as working in education is all i know , and if we are excluded from society that excludes a hell of a lot of jobs that i could do but would be deemed unsuitable for if i am pos .

    think ill just concentrate on the getting well bit and actually having a life again before even thinking about work .
     
  10. V99

    V99 *****

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    Simply, they need to do more research now (Governments that means you) so they see how they can stop the spread.

    Overstressed - I take your point though, but the chance of getting better outweighs this issue for me. The current situation really is incredible.
     
  11. Cookie Monster

    Cookie Monster

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    I agree, i think for myself it comes down to having an overbearing desire to want to feel well again. Im not prepared to let other people's misguided prejudices come before that, plain and simple.

    Many people are currently unable to work, or to sustain a relationship. They have been abandoned by alot of their close friends because they cannot keep up with regular social events and many have to live off of inadequate benefits. Help for these people i feel should be given highest consideration.

    With regards to the link on the first post to this thread - i could access it last night, however today its not working for me - is anyone else having a problem with it?
     
  12. lansbergen

    lansbergen Senior Member

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    None of the links are working anymore.
     
  13. Gerwyn

    Gerwyn Guest

    XMRV can be like a mouse in your basement quiet and you would not know irwas there unless you went looking.It can also be like rats in the loft,nothing too serious but a damn nuisance.Xmrv can also be like a rampageing horse trahing your living room.Finally it can be like a heard of elephants totally demolishing your house.it all depends on how w ell the house was protected(apart from the last bit)
     
  14. JillBohr

    JillBohr Senior Member

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    I was having this discussion with other parents that have children with autism. There is a cluster of teachers in NJ that taught special ed and they have a huge rate of children with autism. They did building inspections etc. to see if it was something in the environment. There was a paper published, Natasa sent this to me (again, thank you Natasa) that mentioned it may be a viral cause. Many of us parents are worried that if our kids do have XMRV, many people will not want to work with them. It is a tough situation. I have many gay friends and I never question if they are HIV positive or not. It does not even come to my mind. However, I do not have to worry about them biting me. It is a different story when working with aggressive children on the spectrum.
     
  15. coxy

    coxy Senior Member

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    I've had in my mind for quite sometime about what will happen once the XMRV thing gets out into the general population. My gp hasn't even heard about it at the moment so we have to bear in mind although we are becoming experts on it, most of the population don't even know it exists, but that hasn't stopped be telling my husband not to discuss it with his friends etc incase it all goes public soon.

    I worry that the schools our healthy 2 children are at would suddenly become concerned that the children could be carrying something, other parents may become worried about their children mixing with them etc. We have had to inform the schools about their ill brother and sister as it has affected the healthy twos schooling over the years. The schools have always been brilliant to us so far, helping as much as possible to make our life easier, but i feel things could easily change if we get some headlines in the papers linking ME & XMRV, discussing ways it is spread etc.



    The other thing that really worries me is the effect this will have on the 2 healthy children, not so much our 5 yr old because he won't understand, but our 13yr old daughter who is healthy, when she sees the headlines she will naturally think she's next to get ill. The whole situation is fraut with problems and upset from my point of view!

    I'm sure there are many of you that are worried about such issues.
     
  16. Megan

    Megan Senior Member

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    I also am worried about the saliva thing. But what I find odd is that EBV is also transmitted by saliva and something like 90% of the population have antibodies to that (showing prior exposure). If XMRV was so easily transmitted this way then why would we not see a similar infection rate in the healthy population?

    This would imply 2 things to me:
    1) either it's not easily transmitted by saliva (or the other fluids mentioned) even if theoretically possible
    2) we have more to hear on the antibody levels in the healthy population (I note this question was avoided). If these turn out to be much higher that the original 4% we would have less worry about being lepper's, but then we would also lose our association between CFS and XMRV and maybe our 'cause' of the illness.

    But then again I'm not an epidemiologist (did i spell that right?). I am hoping for number one.
     
  17. lansbergen

    lansbergen Senior Member

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    Mayby the server can not cope with the high demands.
     
  18. JillBohr

    JillBohr Senior Member

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    O.K. I got video! Our precious bodily fluids. It is amazing you came up with this before I did. Dr. Strangelove was one of the greatest movies of all time. Peter Sellers is so awesome.

    http://www.youtube.com/watch?v=N1KvgtEnABY
     
  19. VillageLife

    VillageLife Senior Member

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    The news letter from WPI seems to have been removed! http://www.iacfsme.org/Portals/0/pdf/IACFS-Attachment4-April2010.pdf


    also,

    What is meant by a co-pathogen ??
     
  20. natasa778

    natasa778 Senior Member

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