CATCH-22

You know the body-sniffing dogs that search for survivors in the rubble after buildings collapse? You know how the dogs’ handlers hide healthy people in the rubble to prevent the dogs from becoming too discouraged when the dead-body count starts piling up like so many sacks of potatoes?  That’s along the lines of how things have been going ME/CFS, with a bit of bright news followed by crashing blows for patients, who carry on much like their canine counterparts. The fallout can be worse than the original event.

In the U.K., for example, the NICE [National Institute of Health and Clinical Excellence] Guidelines issued in 2007 signaled to patients that they’d have a tough time finding physicians to treat them with more than antidepressants and cognitive therapy.  But the NICE guidelines also put the kibosh on pharmaceutical research into a promising ME/CFS antiviral drug, Isoprinosine.

A 2010 Newport Pharmaceuticals Limited email obtained by CFS Central stated that the company ceased drug trials of Isoprinosine not because the drug was not effective—a preliminary study on ME/CFS patients indicated that it was efficacious—but solely because of the NICE Guidelines, which, stated the memo, “advocated non pharmaceutical intervention for the treatment of the condition.”

Isoprinosine has proved helpful for some patients with ME/CFS. Several physicians have treated ME/CFS patients with  Isoprinosine, including Dr. Nancy Klimas in the U.S.  It’s believed the drug works as an immunomodulator, by shifting humoral (antibody) Th2 dominance into cell-mediated Th1 dominance, which rallies macrophages, natural-killer cells and cytotoxic T-cells.  Natural killer cell function is usually depressed in ME/CFS patients. In studies, the drug has been show to prevent HIV patients from developing AIDS, and has also been used to treat cancer.  It’s approved in Europe and Canada to treat viral infections. Once a drug is approved for a specific disease, it lends legitimacy to that disease.    

CFS Central queried Newport Pharmaceuticals with a list of questions:

• Why did Newport Pharmaceuticals decide to investigate Isoprinosine to treat ME/CFS?

• The company conducted a Phase II trial in Canada in 2003: “Clinical improvement in chronic fatigue syndrome is associated with enhanced natural killer cell-mediated cytotoxicity: The results of a pilot study with Isoprinosine.” Did Newport Pharmaceuticals conduct any other Isoprinosine drug trials with ME/CFS patients? If so, I’d be interested in reading those studies and knowing the results.

• The ME/CFS Isoprinosine research stopped due to the NICE guidelines, which advocates using only antidepressants, GET [Graduated Exercise Therapy] and CBT [Cognitive Behavioral Therapy] to treat ME/CFS patients. What year did Newport terminate the ME/CFS research into Isoprinosine?

• Would you explain why your company decided to stop the research because of these guidelines?  After all, treatment guidelines change over time, and research into new drugs is one of the ways that they do.

• If the drug wouldn’t work for the U.K. market due to the NICE guidelines, why not for the American market, the Canadian market, or those of other countries?

• Are there any plans to investigate whether Isoprinosine inhibits the retrovirus XMRV in patients with ME/CFS or prostate cancer?  As you may know, the newly discovered retrovirus has been found in patients with both diseases.  

The company declined comment.

Research guidelines and treatment guidelines are two different things—or should be:  Today’s experimental treatments often morph into tomorrow’s standard of care. ME/CFS patients can't get effective drug treatments until the research is done.  But the research isn't being done because the government in Great Britain appears all too willing to sweep ME/CFS under the proverbial rug, and at least one pharmaceutical company seems willing to follow.  

Dr. Coffin Responds

While waiting for sources to get back to me, I thought I’d post preliminary comments from Tufts University’s Dr. John Coffin.  Coffin co-authored two of the four studies in Retrovirology on Monday that postulated that XMRV may be merely contamination from mouse DNA, as opposed to a new human retrovirus that has jumped species from mouse to man and has been found in patients with ME/CFS and prostate cancer.

CFS Central:  In your papers, you write that you obtained samples of WPI's [Whittemore Peterson Institute] XMRV positive lymphoblastoid cells.  Your papers, however, don't discuss testing these cells for evidence of mouse DNA….  Did you test these cells for evidence of mouse DNA?  If so, did you find contamination? If you did not test the 1282 cells for contamination, why did you decide not to test them?

JOHN COFFIN:  Not to my knowledge, since there was no particular reason to do so.  We have tested [prostate cancer] 22Rv1 cells, and some other human cell lines, with negative results.

CFS Central:  Were the cell lines you tested that had no mouse contamination (the 22Rv1 cells, for instance) XMRV positive or XMRV negative?

JOHN COFFIN:  22Rv1 is XMRV positive. It's the standard positive control.

CFS Central:  Have you tested or do you have plans to test XMRV positive patient samples from WPI or MLV [-related virus] positive patient samples from Drs. Alter and Lo?  

JOHN COFFIN:  We have no plans to do so at Tufts. However, the group I work with in the NCI [National Cancer Institute] is collaborating with the Blood Working Group, and we will look at samples from both the WPI patients as well as the same patients that Lo and Alter studied. [Lo and Alter are the principal investigators of the NIH/FDA/Harvard study published in August, which found XMRV-related retroviruses in the majority of ME/CFS patients and 7 percent of controls.]

CFS CENTRAL:  If you’ve already tested these retroviral positive samples from WPI and Alter/Lo, did you find mouse DNA contamination?  

JOHN COFFIN:  We haven't done that yet.

CFS CENTRAL:  If Tufts hasn’t tested these samples and has no plans to, wouldn’t that be the definitive way to determine whether there is mouse DNA contamination?

JOHN COFFIN:  We will test at NCI using the same assay.

Contamination?

I’m working on a piece about Monday’s Retrovirology papers that postulated that XMRV was merely lab contamination from mouse DNA rather than an authentic, new human retrovirus.  Please bear with me.

Disability Claims

 Linda Nee heads up Disability Claims Solutions, which helps ME/CFS patients in the U.S. and the U.K. apply—and if need be fight—for long-term disability.  

“Many insurance companies have the philosophy that they predetermine the outcome of ME/CFS claims—and that outcome is to deny the claims,” Nee says matter-of-factly.  Should the insurance company pay the claim, she says, there’s an enormous financial advantage to categorize ME/CFS as a psychological problem.  Group policies in Europe and the U.S. often cover psychiatric disorders for only two years, whereas coverage for a physiological disease usually continues until age 65. 

“You do the math,” Nee says.