Dr Pall is the founder of the NO/ONOO theory of the cause of CFS, as well as a number other disease states.
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I've been incommunicado for quite a while, working on three things, two of which I will probably share with you a bit later. There were questions raised about the XMRV association with CFS/ME found by Judy Mikovits and her colleague in Nevada and elsewhere, so I wanted to summarize where we are on that, as best I can determine. You are welcome to share these comments elsewhere, if you wish.
Mikovits and her colleagues published a paper and accessory materials in the journal Science, a highly respected journal and have also provided additional and in some cases more recent information elsewhere.
In the Science publication they report that the XMRV retrovirus occurs in about 2/3rds of CFS/ME patients but only in 3.7% of normal controls. They also report that subsequently, using a more sensitive assay, XMRV occurs in over 90% of CFS/ME patients - we don't know what the percentage is for normal controls using that more sensitive assay.
The virus was originally isolated from some aggressive prostate cancer cells. In addition, in unpublished data, it is also apparently shows high prevalence in fibromyagia patients and in atypical multiple sclerosis (MS) patients.
Comment: These data apparently show that XMRV is not specific for CFS/ME but rather occurs in other disease states, as well as in some normals.
My own view is that this makes it much more likely to be an opportunistic disease, caused by the changes in immune function and other properties of these diseases, rather than a primary cause.
Specifically, the retrovirus, based on its DNA sequence, has its replication stimulated by NF-kappaB activity, an activity that is elevated as part of the NO/ONOO- cycle and has been reported to be elevated in CFS/ME.
Furthermore, the low NK cell activity and other types of immune dysfunction, that occurs in these various diseases, may also be expected to stimulate the ability of the virus to maintain itself in disease sufferers.
In order to show that it is the primary cause of CFS/ME, it is necessary to show that XMRV follows Koch's postulates, but so far it does not apparently follow Koch's first postulate, which requires that it always occurs in people with the disease but does not occur in normals. The other three Koch's postulates have not been tested.
In contrast to that, we have a good fit to the five principles underlying the NO/ONOO- cycle for both CFS/ME and fibromyalgia. Because one can argue that the fit to these five principles serve very much like Koch's postulates for NO/ONOO- cycle disease, I will argue that we have a substantially more compelling case for a NO/ONOO- cycle etiology than we do for an XMRV infectious etiology for either CFS/ME or fibromyalgia.
That does not mean that XMRV is unimportant, however. Even if it turns out to be an opportunistic infection, like mycoplasma and HHV-6 are, it still may contribute to the etiology of the disease.
And it still raises the question of whether we can cure cases of CFS/ME and fibromyalgia simply by normalizing the NO/ONOO- cycle as opposed to normalizing it and also using antivirals to depress XMRV and/or HHV-6. This is a question and I don't claim to have the answer to it, although my hope is that normalizing the cycle will also cure at least some of these infections, that may not be true.
There have been comments in the media to the effect that this finally shows that CFS/ME is physiological, not psychological. This is true, but this should have been obviously true anyway, at least six or seven years ago.
Nevertheless the media coverage of CFS/ME obtained by Mikovits and her colleagues must be viewed as a true gift to those interested in extending public knowledge of this disease.
Martin L. (Marty) Pall
Mikovits and her colleagues published a paper and accessory materials in the journal Science, a highly respected journal and have also provided additional and in some cases more recent information elsewhere.
In the Science publication they report that the XMRV retrovirus occurs in about 2/3rds of CFS/ME patients but only in 3.7% of normal controls. They also report that subsequently, using a more sensitive assay, XMRV occurs in over 90% of CFS/ME patients - we don't know what the percentage is for normal controls using that more sensitive assay.
The virus was originally isolated from some aggressive prostate cancer cells. In addition, in unpublished data, it is also apparently shows high prevalence in fibromyagia patients and in atypical multiple sclerosis (MS) patients.
Comment: These data apparently show that XMRV is not specific for CFS/ME but rather occurs in other disease states, as well as in some normals.
My own view is that this makes it much more likely to be an opportunistic disease, caused by the changes in immune function and other properties of these diseases, rather than a primary cause.
Specifically, the retrovirus, based on its DNA sequence, has its replication stimulated by NF-kappaB activity, an activity that is elevated as part of the NO/ONOO- cycle and has been reported to be elevated in CFS/ME.
Furthermore, the low NK cell activity and other types of immune dysfunction, that occurs in these various diseases, may also be expected to stimulate the ability of the virus to maintain itself in disease sufferers.
In order to show that it is the primary cause of CFS/ME, it is necessary to show that XMRV follows Koch's postulates, but so far it does not apparently follow Koch's first postulate, which requires that it always occurs in people with the disease but does not occur in normals. The other three Koch's postulates have not been tested.
In contrast to that, we have a good fit to the five principles underlying the NO/ONOO- cycle for both CFS/ME and fibromyalgia. Because one can argue that the fit to these five principles serve very much like Koch's postulates for NO/ONOO- cycle disease, I will argue that we have a substantially more compelling case for a NO/ONOO- cycle etiology than we do for an XMRV infectious etiology for either CFS/ME or fibromyalgia.
That does not mean that XMRV is unimportant, however. Even if it turns out to be an opportunistic infection, like mycoplasma and HHV-6 are, it still may contribute to the etiology of the disease.
And it still raises the question of whether we can cure cases of CFS/ME and fibromyalgia simply by normalizing the NO/ONOO- cycle as opposed to normalizing it and also using antivirals to depress XMRV and/or HHV-6. This is a question and I don't claim to have the answer to it, although my hope is that normalizing the cycle will also cure at least some of these infections, that may not be true.
There have been comments in the media to the effect that this finally shows that CFS/ME is physiological, not psychological. This is true, but this should have been obviously true anyway, at least six or seven years ago.
Nevertheless the media coverage of CFS/ME obtained by Mikovits and her colleagues must be viewed as a true gift to those interested in extending public knowledge of this disease.
Martin L. (Marty) Pall