Article: Four Viruses! Alter Paper Confirms Retroviral Findings in CFS

You can view the page at http://www.forums.aboutmecfs.org/content.php?213-Four-Viruses-The-Alter-XMRV-Paper-Arrives

 

"Will the real CFS patients, please stand up. Oh, wait, I see you can't. Well, just send me an e-mail."

Tina

:Sign Good one:

 

Excellent summary Cort. You have a real gift in science translation! (Imagine what you are going to be able to achieve once the XMRV/MLV/CFS/ME is cured!)

Question: Given that the WPI are now also finding more variation and different types of MLV's (if I understood correctly) in their patient cohorts, rather than just pure XMRV, that might beg the question - does true XMRV exist any more, or has it mutated already?

From Tuesday's FDA/NIH/CDC conference (transcript on Facebook prepared by Parvofighter and Global XMRV action) 23rd Aug:

Dr Lo: "Retroviruses use the RT, the reverse transcriptase and that is an enzyme that the fidelity is not very good so each time when they replicate they very easily introduce a different kind of a mutation. So after the infection certainly they can also start to accumulate this kind of mutation or changes."

Dr Alter: "To demonstrate that further we in our paper, we recalled 8 patients from Dr Komaroff. 15 years later 7 of the 8 still had the virus but the virus had changed within the patient over that time. These are minor variations, very characteristic of the mutation in the patient. And again suggest that this is a real phenomenon in the patient and not a laboratory contamination."
...

Also, does mutation in the patient potentially explain different symptom clusters in different patients, and symptom changes in the same patient over time?

 

A question to ponder for scientists examining XMRV in future research studies:

Re: Mitochondria/ energy production -
Even HIV patients responding well to ARV drug therpay do not necessarily lose their fatigue - if I remember correctly - so there is a huge missing link still.

What is the food source for XMRV and related MLV's?
Is it fatty acids (ie from cell walls and brain/nervous tissue), cholesterol or ? (fill the gap), and will that help for targeting drug treatments ie by interfering with the retroviruses ability to feed itself and reproduce?

Hell, these retroviruses steal our energy/ life force, why not return the favour/favor?

 

FDA vs CDC on XMRV results

To make things even crazier they report that the CDC samples they tested were negative for XMRV as well.

I'm not sure this is inconsistent, given that Lo/FDA found MLVs but not XMRV. The precise wording used on the FDA website to report their negative XMRV findings for CDC samples is interesing (my italics below):

Initial analysis shows that the FDA test results are generally consistent with CDC, with no XMRV-positive results in the CFS samples CDC provided (34 samples were tested, 31 were negative, 3 were indeterminate)

So the FDA found no XMRV in their own samples and none in the CDC ones either. But did the FDA find any evidence of MLVs in the CDC samples? that might tell us more.

And do we generally need fewer acronyms in CFS research?

 

Severity of illness important?

"Of the 37 patients in the Alter study, 25 came from Dr. Komaroff's clinic, and the other 12 came from the practices of David Bell and Paul Cheney. (Komaroff was able to confirm that of the 25 patients from his clinic, all 25 met the 1988 Holmes criteria for CFS, and 21 of those 25 also met the 1994 Fukuda criteria. No information was provided on the criteria applicable to the other 12 patients.)"

Lots more we still have to learn and analyze about the cohorts.

Thanks for the analysis and clarifications, Anika.

I did wonder if severity of illness was a factor in these results? The Lo study notes "virtually none [of thier patients] had any regular social contact" and I think, though can't find the relevant bit, that the Lombardi Science paper similarly claimed that their patients were quite severely affected. Certainly this level of illness is far more than required by the 1994 CDC (Fukuda) - let alone the wacky 2005 CDC Empirical criteria - so perhaps the two positive findings have come using particularly sick/severely-affected CFS patients?

Also, the 1988 Holmes criteria requires at least 50% impairment in activity while the 1994 fukuda criteria simply require undefined 'substantial' impairment.

Separately, I'm surprised that some of Komaroff's patients met the Holmes criteria but not the Fukuda criteria, but it does support your idea that the 'looser' criteria may actually exclude some CFS patients.

 

i think the HIV drugs themselves damage mitochondria

 

Dr Alter: "To demonstrate that further we in our paper, we recalled 8 patients from Dr Komaroff. 15 years later 7 of the 8 still had the virus but the virus had changed within the patient over that time. These are minor variations, very characteristic of the mutation in the patient. And again suggest that this is a real phenomenon in the patient and not a laboratory contamination."
...

Also, does mutation in the patient potentially explain different symptom clusters in different patients, and symptom changes in the same patient over time?

Well, here we are... Three decades after HIV and retroviruses, some researchers felt the need to state that XMRV was a 'simple' virus. Retroviruses mutate, mutate very quickly, and so most likely XMRV does. I think we can leave out 'healing', that's out of the question - certainly if we look at the HIV pandemic. Yes, people do not die, but are forced to take their meds, every day until they die(because of the meds).

OS(very cynical).

 

" Although three MLV’s were found one MLV dominated the rest, infecting 86% of the CFS patients."
Is that a typo ? 86% was also exactly the total % of ME patients with any MLVs.
or does that mean that some patients had more than one type of MLV.

Other thoughts: Does the "not exactly XMRV" result tie in with earlier comments by Mikovits about some kind of editing being done by the cell's defences. Is it possible that slight variations in procedure/timing either allow the editing to complete, or retain the pre-edited pure XMRV (original study). I look forward to Mikovits and other researchers soon sharing their interpretations just like after the 2009 Science publication.

re: Mitos.... I sure would like more investigation into them also. Too bad the Myhill study wasn't followed up - it would be nice biomarker(s) to match up to the results being published.

 

Well, here we are... Three decades after HIV and retroviruses, some researchers felt the need to state that XMRV was a 'simple' virus. Retroviruses mutate, mutate very quickly, and so most likely XMRV does. I think we can leave out 'healing', that's out of the question - certainly if we look at the HIV pandemic. Yes, people do not die, but are forced to take their meds, every day until they die(because of the meds).

OS(very cynical).


Not so very cynical, OS. Yes, AIDS patients require meds, very expensive meds. Combine today's recession with sky-rocketing health costs, medicare cuts, the price of insurance premiums, powerful insurance lobbyists, boomers who are going to hit medicare like no other generation before, and ask yourself are we in any better position today for another AIDS epidemic? Call me cynical, but I think it's going to be a long time before help comes our way -- insurance paid help. Best bet, get in a drug trial.

 

Oh, I left out disability insurance. Surely with these scientific advances and more to come, it won't be so easy to deny disability. How healthy is Social Security? Don't forget those boomers nearing retirement age.


Cort, congratulations on a job well done. Excellent article! It's very easily understood by the layman. Thanks.

 

Great article, Cort!

I've been trying to keep track of the cohort used in this study, hoping to post a summary backed up by authority. Not ready for prime time yet...

But, I can note one correction that could be made in your article - where you state "The Alter study participants were provided by Dr. Komaroff from patients at his clinic. (Interestingly only half of them met the Fukuda criteria while all met the Holmes criteria.")

It would be more correct to say: "Of the 37 patients in the Alter study, 25 came from Dr. Komaroff's clinic, and the other 12 came from the practices of David Bell and Paul Cheney. (Komaroff was able to confirm that of the 25 patients from his clinic, all 25 met the 1988 Holmes criteria for CFS, and 21 of those 25 also met the 1994 Fukuda criteria. No information was provided on the criteria applicable to the other 12 patients.)"

I don't think the information about the source of the 12 non-Komaroff patients was in the PNAS paper - I think it was mentioned by McCleary in her good article, which looked back to the 1993 paper on mycoplasma fermantans that was published on these patients.

Also note - of the 25 Komaroff sample patients, 24 of 25 (96%) were positive according to the PNAS paper. This must mean that 8 of 12 of the Bell or Cheney patients (67%) were positive (implied not stated).

Lots more we still have to learn and analyze about the cohorts. But, I have seen some commentators express concern that with each "looser" case definition of CFS, there is not only an issue of bringing in people who wouldn't meet more "stringent" definitions, but there is also an issue of losing from the case definition people who meet the "stricter" criteria.

Anika

Thanks Anika, I fixed them both. I thought it was so weird when I wrote that that only half met the Fukuda criteria - now I don't know how I got that into my head. Thanks for pointing that out.

 

Not so very cynical, OS. Yes, AIDS patients require meds, very expensive meds. Combine today's recession with sky-rocketing health costs, medicare cuts, the price of insurance premiums, powerful insurance lobbyists, boomers who are going to hit medicare like no other generation before, and ask yourself are we in any better position today for another AIDS epidemic? Call me cynical, but I think it's going to be a long time before help comes our way -- insurance paid help. Best bet, get in a drug trial.

You're right, time to 'heal' the people, don't you think ? But who's going to stand-up against Big P ? Not only there's a health problem to solve, there's a politcal one too.

My point was actually that I want to get rid of this retrovirus, I don't want it inside me, and pass it on to people. But looking at the HIV pandemic, we will get at best, meds to keep the virus at bay...as long as you swallow the pills.

OS.

 

Anika, I love your idea of the cohort summary. One thing to consider is that these were pre-filtered patients, either self-selected to some of the best biological ME/CFS practitioners in the US at the time, and/or also screened extensively by these ME/CFS physicians "in the know". So while they did indeed meet the Holmes and/or Fukuda criteria, they also undoubtedly met the unofficial "Komaroff, Cheney, and Bell Criteria".

.

Good point. I think the Komaroff, Cheney and Bell Criteria idea is a great one and could be a key issue in all this. One other thing - when physicians provide patients for studies they often cherry pick them - they provide the most characteristic (ie without alot of other diseases) or the cleanest ME/CFS patients they have. The ones they are most sure of - so you may have another filter as well.

 

Great article, Cort. The best of what Cort Johnson does best. You not only translate the paper into plain English, you explain the implications of the findings. This is what has made me a PR fan for years.


Actually the slide just before that one specified that it was whole blood spiked with XMRV positive cells, and plasma spiked with supernatent containing XMRV cells. I think it was also mentioned at the Blood Products Advisory Committee meeting.

Thanks! I updated it to make that more clear.

 

I'm not sure this is inconsistent, given that Lo/FDA found MLVs but not XMRV. The precise wording used on the FDA website to report their negative XMRV findings for CDC samples is interesing (my italics below):



So the FDA found no XMRV in their own samples and none in the CDC ones either. But did the FDA find any evidence of MLVs in the CDC samples? that might tell us more.

And do we generally need fewer acronyms in CFS research?

Wow! Good point. They didn't say anything about MLV's! There are layers and layers. That is interesting...I'll bet they didn't because they are preparing a paper on that. Hmm......

 

" Although three MLVs were found one MLV dominated the rest, infecting 86% of the CFS patients."
Is that a typo ? 86% was also exactly the total % of ME patients with any MLVs.
or does that mean that some patients had more than one type of MLV.

Other thoughts: Does the "not exactly XMRV" result tie in with earlier comments by Mikovits about some kind of editing being done by the cell's defences. Is it possible that slight variations in procedure/timing either allow the editing to complete, or retain the pre-edited pure XMRV (original study). I look forward to Mikovits and other researchers soon sharing their interpretations just like after the 2009 Science publication.

re: Mitos.... I sure would like more investigation into them also. Too bad the Myhill study wasn't followed up - it would be nice biomarker(s) to match up to the results being published.

You can check more on the editing in "A New Kind of XMRV" . Dr. Alter hasn't talked about that yet but it certainly seems like it fits. The WPI's was able to find XMRV without worrying about editing in the original group of patients. My guess is that they had a harder time finding it after that and after the editing paper came out they starting looking more at 'variants' and that helped them substantially. In any case the DHHS Working Group is apparently well aware of that and is checking it out.

 

Well, the best news of all is that they are becoming more focused on a viral cause and no longer trying to hide us and sweep us under a rug. At least, not nearly as much. They are now actively looking for a real biological cause. So in the next few years, maybe we will finally get a real breakthrough. I think things are looking up for once.

 

Thanks Cort, we are on track.

 

A PS. Please may I add from a ten yearer (very restricted but some at last sense of humour returned) quote Spike Milligan "I told you I was ill" . Hope findings CDC/Harvard will ban blood donation and put the wind up our IDIOTS in the UK.

 

Anyone know where we can write a thanks / congrats card to this team?
People on the ground doing this research do not know quite how important they are, nor how few and narrow the roads out of the disease are past the 2 year mark. You can get national adulation - and a few million - by having being an entertaining party-animal with good abs and landing in the right situation, but doing something truly valuable earns you the right to scramble for another grant with a salary about equal to beer money on Wall Street. They deserve better, maybe it can start with us.