Are Singh and Bateman Afraid of Proof of Principle Studies? Why?

“Our findings do not support an association between CFS and MLV-related viruses including XMRV and off-label use of antiretrovirals for the treatment of CFS does not seem justified at present.^”

^{-Dr. Ila Singh et al}

^{http://jvi.asm.org/cgi/content/abstract/JVI.00693-11v1}

^{After yet another study purporting to look for HGRVs such as MLVs and XMRV in ME/CFS patients but not following the exacting protocols of the original Lombardi et al study published in Science in 2009, nor those of the Alter/Lo study, the scientific conclusions of this study were predictable. The question still unanswered: When will researchers actually replicate the original study they seek to refute? And how can they, in scientific honesty and in good conscience, keep claiming to refute the study they refuse to actually replicate?}

^{And why add the editorial and unscientific comment attempting to discourage proof of principle studies? Is it about your patent applications, Dr. Singh?  From April 7, 2011 publication of her patent application:}

Title:

COMPOSITIONS AND METHODS FOR TREATING MLV-INFECTION, AND PREVENTING AND TREATING MLV-INITIATED DISEASES

Abstract:

Compositions and methods for inhibiting infection by XMRV or other MLV are disclosed. Also disclosed are methods for treating cancers resulting from infection by XMRV or other MLV, and for preventing such cancers. The anti- XMRV/anti-MLV compounds are predominantly integrase inhibitors, such as globoidnan A, L-000870812, S/GSK1349572, S/GSK1265744, Raltegravir and Elvitegravir, and also reverse transcriptase inhibitors AZT, tenofovir, and tenofovir DF. The compounds are also useful for treating chronic fatigue syndrome or other diseases with neuroimmune symptoms resulting from an infection by XMRV or other MLV. The compositions can also include other therapeutic agents known for treating prostate cancer, breast cancer, lymphomas, and leukemias, such as anti-androgenic agents, radioisotopes, and conventional anti-cancer compounds.

^{What Is “Proof of Principle”?}

^{See my earlier post: http://biomedicalmecfs.blogspot.com/2011/01/xmrv-proof-of-principle-studies.html}

^{In short, proof of principle studies, in the case of ME/CFS, would treat a cohort of patients who have been diagnosed with the illness by competent physicians and, preferably, who have tested positive for XMRV and/or other MLVs/HGRVs, with antiretrviral drug “cocktails”, perhaps in combination with other antiviral drugs to treat some of the co-infections such as those found by Dr. Montoya at Stanford. Another possible combination might include Ampligen.}

^{Dr. Singh herself has already found that at least 3 of the ARVs considered safe enough for HIV/AIDS patients, are effective against XMRV in the lab. Is she afraid that ME/CFS patients will use this information to justify trying to save their own lives by trying those drugs? And if they come to harm, that they would blame her? That doesn't seem logical to me, but I'm trying to understand why she would come out against proof of principle trials and I can't think of any scientific reason. It has been obvious since the mid-1980s, from the brain scans of the Incline Village patients, that the disease is associated with a retrovirus and/or virus(es). Not knowing specifically which RV or virus is no excuse for not treating for them.}

^{She and her collaborators seem to have bought, or wish to promote, the establishment stereotype of ME/CFS patients as a bunch of uninformed fanatics, so desperate that they would harm themselves for no reasonable chance of improvement. Surely she is aware that any patient who tries “off-label” use of antiretroviral drugs to treat the retroviruses associated with ME/CFS are not getting these drugs without the support and assistance of their own physicians. Why accentuate the “risks”, which are acceptable for other patients with retrovirus-associated diseases such as AIDS, without acknowledging the potential benefits? The risks are well known and physicians are doing the tests and surveillance required, so they don't need to be cautioned by researchers. The cautions appended to this study create a murky atmosphere and lead to suspicions of ulterior motives by this group of researchers. At best, it only serves to support the CDC's mantra, there are no tests for ME/CFS, there are no treatments for ME/CFS. Chant three times for maximum inculcation.}

“...off-label use of antiretrovirals for the treatment of CFS does not seem justified at present.^”

^{-Dr. Ila Singh et al}

^Justified?

^{What a curious assessment and what an arrogant, giant leap of logic!}

^{Why should Dr. Singh, the Drs. Light and Bateman make this judgment for others who are equally, or better informed than they are on the subject?}

^{Does anyone actually think that Dr. Snyderman and Dr. Deckoff-Jones should have just accepted their “fate” while waiting for researchers to do the “science” in their own sweet time? See their takes on the subject on her blog: http://treatingxmrv.blogspot.com/}

^{Each of these physicians with personal knowledge of the disease, the research and the potential treatments and side effects came to the conclusion that intervention was and is “justified”. Each has experienced substantial improvement in quality of life. It may even be that Dr. Snyderman has saved his own life, or at least prolonged his survival.}

^{As a cancer researcher, Dr. Singh ought to be more cognizant than she appears to be of the association of all known retroviruses with immune dysfunction and rare cancers, which turn out to be not so rare in ME/CFS patients. This is just one of many similarities that ME/CFS shares with HIV/AIDS. Surely Dr. Singh is not so young or so uninformed that she does not know that early drug interventions were trialed in AIDS before all researchers were convinced that HIV was the cause.}

^{To tell ME/CFS patients like Dr. Snyderman and Deckoff-Jones, and all the rest of us, that we should keep experiencing disease progression, the deterioration in quality of life, the impoverishment, degradation and premature death that comes with having a debilitating illness that has not been dealt with in a scientific, ethical or pragmatic manner for so many decades is incomprehensible to me. It seems like an underhanded swipe at the translational medicine and research of those scientists and physicians at WPI and the University of Nevada, who are collaborating to save lives right now, not in some distant future when “consensus” has arrived.}

<sup>I have to wonder if she would have said the same thing to my mother when she was pressured by her doctor to trial tamoxifen, an unproven cancer drug that patients had to pay for themselves since it was deemed “experimental”. Why is it OK for AIDS patients and cancer patients to try “experimental” or “off-label” drugs when the alternatives can only offer an earlier death or further disease progression?

Why is Singh's co-author, Dr. Bateman, getting involved in the pay-for-treatment study of Ampligen which could be described, in part, as an antiretroviral drug? Who but ME/CFS patients will participate in this study? Hemispherx has said that those who test postive for XMRV have a higher success rate than those who don't.</sup>

^{The conclusions of this study might as well have been “...treatment of CFS does not seem justified at present.”}

^{The only “advancement” of science this study provided: more proof that no one will find the retroviruses WPI found unless and until they actually REPLICATE the study. Just going through the motions without actually REPLICATING the original study does nothing but waste money and, more importantly for me, time.}

^{The ethical, moral and scientific questions I pose to Dr. Singh and her collaborators are these: Why didn't you replicate the WPI study? Why do you engage in this double standard of attitude and treatment of ME/CFS patients vs. those with other diseases?}

XMRV Deja Vu: Dr. Bell's Appeal to Fund WPI Is Still Pertinent, 8 Months Later

McHumor Cartoons

On May 1st, 2010, Dr. David Bell issued a call to patients and those who care about them to donate to WPI. His assessment of the situation was right on target then and it still is.

WPI's youtube videos: one has Dr. Deckoff-Jones speaking
                                                                              

David S. Bell MD, FAAP
Lyndonville, NY 14098

May 1, 2010

To my friends with ME/CFS,

I would like to put out a personal appeal for funds to be sent to the Whittemore Peterson
Institute (WPI) in order to speed up the progress of the current research. Here is my reading of a
very complex situation.

Medical authorities, educational institutions, governmental agencies, and most practicing
physicians have disrespected and minimized CFS in just about every way possible, from creating
an insulting name for the illness to advising extreme caution in treatment, except cognitive
behavioral treatments.

It is easy to dismiss my remarks to follow by saying that I am biased. And it is true, I am
very biased and for twenty five years I have quietly sat on the sidelines believing that science
will win out and true progress will be made. I am beginning to think this has been a great
mistake. The profession I love has failed miserably.

In 1985 an outbreak of CFS hit Lyndonville NY and affected 210 persons, 60 of whom
were children. The official response from the CDC and the New York Health Department was
that this was mass hysteria. No one talked with a single patient. In 1990 I worked with Dr. Elaine
DeFreitas and Dr. Paul Cheney and a retrovirus was found and the material published(1). A
second paper had been accepted by PNAS and contained a photograph of C-type retroviral
particles from a tissue culture of spinal fluid of one of the children in the Lyndonville outbreak.
This paper was suddenly pulled and not published after a couple of flawed negative papers. A
complete description of these troubled times is in Osler'sWeb by Hillary Johnson. The funding for
our studies was pulled and all work on this abruptly stopped.

I think the same tactics are being employed to hamper the current work on XMRV by the
WPI. The WPI is a private organization and, as I understand it, no federal grants or funding has
been forthcoming. There have been three negative PCR-only studies which have established only
that CFS can not to be superficially studied. At this time no study that has attempted to replicate
the WPI study has been heard from. Many CFS research organizations have declared publicly
that "XMRV is a dead issue."

Nothing is farther from the truth. I cannot predict the future, but my fear is that the
current political and scientific organizations who do not want to see retroviral involvement will
attempt to stifle studies on XMRV in CFS. Huge amounts of money are spent on studies on
cognitive therapy, and studies proving that CFS is heterogeneous (you can argue that polio is
heterogeneous).

We have not heard from the CDC, other than the inappropriate comment that this was not
likely to turn out to be anything, made right after the Science paper publication in October 2009.
We are now eight months later and not a peep. Maybe they are finding XMRV and want to be
very careful. Maybe they haven’t looked and are assuming that this heretical idea will blow
away. Eight months?

And the Band Played On.

It is possible that thirty other labs are finding XMRV in CFS or that no one else in the
world is even looking for it. Science requires that labs do not disclose their findings prior to
publication and I agree with this rule. But is the WPI going to be isolated by the scientific
community and wither away because of lack of funding? Is XMRV going to become more of the
compost of CFS research?

But there is an alternative. We cannot wait ten years for science to grind outs its
conclusions. Every person in the world who believes that CFS is important should send $10 to
the WPI. I plan to send $10 today. It may not be much, but it is a start. There may be 10 million
persons in the world with CFS. Lets see, that’s…I need a calculator. May 12 is our day. Lets do
this.

After 25 years of work in this field I do not have much. But I have my integrity. I feel
that WPI has made an important discovery and I feel they are an ethical organization, they are
not padding their pockets. But I also have my fears. And the greatest fear of all is that their
discovery may not be appropriately followed up.

For the 9,999,999 other people out there who think CFS is both real and important, send
$10 to: Whittemore Peterson Institute, 6600 N. Wingfield Parkway, Sparks, NV 89436.

Thank you.
David S. Bell MD, FAAP

1. DeFreitas E, Hilliard B, Cheney P, Bell D, Kiggundu E, Sankey D, et al. Retroviral sequences
related to T-­‐lymphotropic virus type II in patients with chronic fatigue immune dysfunction syndrome.
Proc Natl Acad Sci. 1991;88:2922-6.

                                                                     

Two Physicians Try Antiretroviral Drugs For ME/CFS

ME/CFS is a crippling neuroimmune disease that has ruined the lives of at least a million Americans.

After 20 years of searching for treatment, the parents of Andrea Whittemore, who has had it since she was 12, funded research into the illness. They started WPI, the Whittemore Peterson Institute.

This resulted in the finding in 2009 of a new retrovirus, tentatively named XMRV, in most ME/CFS patients. In 2010 virologists at the FDA, NIH and Harvard published a study supporting the 2009 findings of WPI.

Subsequently, Dr. Ila Singh researched whether any of the drugs developed for the well known retrovirus, HIV, might be effective against the new virus. She found 3 FDA approved drugs that were effective against XMRV in the lab: AZT, Viread and Insentress.

Patients and the doctors who treat them have suspected a virus or retrovirus was the culprit, all or in part, since AIDS-like lesions were found in brains scans of ME/CFS patients in the 1980’s. The relapsing-remitting pattern of the illness also mimics viral illnesses such as malaria or herpes. The profound, disabling exhaustion is reminiscent of infection with Epstein Barr virus. The flu-like symptoms many experienced at onset also infer a viral infection.

Not surprisingly, doctors may also get this disease.

Two who did get it, Dr. Jamie Deckoff-Jones and Dr. Michael Snyderman, in consultation with their own physicians, decided to try the treatments found by Dr. Singh to be effective against XMRV in the lab.

Dr. Snyderman is an oncologist, a cancer specialist, who himself developed a rare cancer that is not that uncommon in CFS patients. He started treatment with AZT and Isentress at HIV doses. He reported that he felt 25% better after 3 weeks. In the 6th month of treatment he added Viread, also at the HIV dosage. At a medical conference he presented a poster detailing his tests, treatment and outcome.

Thanks to Mindy Ketei at http://www.cfscentral.com/2010/10/dr-michael-snydermans-md-anderson.html for that link.

His poster indicates that he no longer tests positive for the XMRV retrovirus and the markers for his cancer have been reduced.

Dr. Deckoff-James was an emergency room surgeon before she became too disabled to work. Last March she began treatment with AZT and soon added Isentress. She and her daughter, who is also disabled with ME/CFS, have blogged about their experiences with the treatment. They added Viread in May. They have shared their ups and downs with their blog readers through the months of overall improvement.

Dr. Deckoff-Jones has said she has improved from approximately 50% functioning to about 80% in the 9 months they have been on these ARV drugs. This has allowed her to go back to work part time. She will be working with Dr. Judy Mikovits, one of the discoverers of XMRV, on a project to educate physicians on how to treat ME/CFS patients who have tested positive for the retrovirus.

Dr. Deckoff-Jones recently overdid it and experienced a "crash" - post-exertional malaise (PEM). She also regrets ever trying to calculate her progress using the KPS (Karnofsky Performance Scale) to estimate her level of functioning. Like many others with CFS, she has found it doesn't do justice to the differences between physical functioning and mental functioning. Many of the details simply do not correlate well to the kind of disabilities CFS patients experience.

Dr. Mikovits is scheduled to report on similar ARV drug treatments by other physicians on January 17, 2011. In a sneak peak at some information that will be shared in Santa Rosa CA on that date. Dr. Timothy Luckett, blogging about ME/CFS, says that "all CFS patients showed remarkable improvements after receiving antiretrovirals - the group that received Viread and Isentress faired out best."

Unfortunately for most ME/CFS patients, these drugs are too expensive. The CDC has declared all tests and treatments for CFS to be "experimental". That means that no insurance program, including Medicare, will pay for them. At a cost of $1200-1500/month plus the costs of seeing a physician who will prescribe them and the monitoring that must be done while taking them, this treatment is out of reach of most ME/CFS patients.

Cartoons by T. McCracken