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Okay, you know what, when you write opinion pieces about gene therapy, or anything medical trial related, you really really need to put your "qualifications" SOMEWHERE.
Case in point. I don't have the time to look up every single detail (though I may depending on whether my annoyance increases or not), but so many things about this article bother me -- and generally, the last one more than the first. This is the original Washington Post article, though it doesn't identify the virus used, so still, I can't totally comment on everything.
I'm going to ignore the specifics of the case since I haven't looked into it and instead deal with the glaring factual errors.
Okay, first off, Humira does not block TNF production nby suppressing the immune system. Humira is a humanized form of Remicaide, and both are ANTIBODIES to TNF. An antibody binds to the soluble TNF in the blood stream and prevents it from activating other cells. A portion of the Remicaide molecule is derived from a mouse antibody. The Humira version has been fully humanized in order to decrease the number of infusion reactions --- which is like a cross between anaphylatic shock and what would happen if you got the wrong blood type. Treatable, but VERY serious and generally precludes you from getting that treatment (or any of the others in the family) again.
Umm, NO. Let me state this very simply, the NIH and the FDA are not going to allow human clinical trials with any virus that can proliferate out of control. There's nothing in the original article that suggests that they found the viral vehicle from the therapy through out the patient's blood stream (not that this isn't possible, but I'm saying it's very unlikely. But I can't say for certain without knowing the exact virus and what had been done to it).
1) They do not know when the patient contracted histoplasmosis.
2) If it spreads beyond the lungs, it is very life threatening.
3) For anyone under immune-suppression, histoplasmosis is very dangerous because it is very easy to spread through the body.
4) Humira suppresses the immune system by soaking up the TNF --- without TNF, it is very hard for your body to start an immune response.
5) According to the WP: "[the patient] was also taking conventional immune-suppressing drugs for her arthritis". Let's see, I'm betting at the least she was taking prednisone. Possibly methotrexate (a chemotherapeutic used for treatment of autoimmune diseases). Either of these alone would have left her vulnerable to infection, add humira, and well...
Now I can hear someone asking, "Well, they shouldn't have let her participate if she was on those drugs". Wrong. First, it's is unethical to withdraw treatment that is controlling a disease to test another treatment. I'm guessing that they were using the experimental therapy on a joint that was continuing to be affected despite her treatment in the hope of maintaining her mobility. Plus, the question is Will the new therapy aid her more than her current regimen. ie, will the addition of this treatment make her even better? The next thing would be to see if this treatment alone could help patients with less severe forms or fewer years of the disease.
The only possible short-sightedness of the protocol is that they should have been monitoring her monthly for opportunistic infections like histoplasmosis, especially given the fact that the fungus is endemic to the area she lives in. But they may have been doing that already, or the test may be less than perfect.
Okay, here's the deal, histoplasmosis is like tuberculosis -- it can lie dormant in the body. We can't say for certain why these organisms reactivate when they do -- Blockers of TNF do contribute because TNF helps cause and maintain the granulomas that wall the bacteria/fungi off from the body. But it isn't unheard of for someone to be fine on immunosuppressants for some number of years before having a reactivation.
1) AGain, willing ignorance of the fact that the patient was on other immunosuppressants.
2) I would like to know the timing of the patient's last Humira injection to comment more on the timing. If the author is getting this just from newspaper articles, they don't know that either.
3) Ertl (declaration: I know this professor in passing, though I doubt she remembers me) is absolutely correct. Virus, like bacteria and cells for that matter, have a set amount of "doubling" time. Most viruses used for gene therapy are also not completely competent to reproduce and are even slower. The post-injection vomiting could not be caused by the therapy -- unless something really screwy went on and the therapy went into an artery or something. Coincidence, really.
I thought I should note when I actually agreed with the author. However, I can understand the clinician's POV --- low grade fever is often a sign of an autoimmune flare. He probably thought that he/she was helping the patient possibly. However, I don't know the standard operating procedures of the trial or anything. But more tests should have been run before the drug was administered.
OMG --- this makes me really question the qualifications of the author -- what science/medical training do they have? Do they know anyone with an autoimmune disease?? Rheumatoid arthritis is a progressive destructive disease that leaves many patients unable to walk without severe pain due to damage to foot and ankle joints, as well as the knees and hips. Not to mention the increased risks for atherosclerosis. Plus, treatments like prednisone increase the risks for stroke and type II diabetes. Stress and infections tend to trigger even more flares making patients captives in their own homes during flu seasons or large gatherings for fear of getting sick. Anyone who knows someone with an autoimmune disease would never say that they are not "serious diseases". And the existing drugs don't work that great, really. Plus, the pain relievers that did help for many -- celebrex etc -- have been removed from the market due to the risk of stroke. I get the lawyer is grandstanding and trying to put on a good face for the lawsuit, but give me a break. The patient probably was starting to face actual constraints in her daily life and had hoped that the trial would really help her and possibly enable her to cut back on some of the medicines she was taking.
Okay, rant over.
Case in point. I don't have the time to look up every single detail (though I may depending on whether my annoyance increases or not), but so many things about this article bother me -- and generally, the last one more than the first. This is the original Washington Post article, though it doesn't identify the virus used, so still, I can't totally comment on everything.
I'm going to ignore the specifics of the case since I haven't looked into it and instead deal with the glaring factual errors.
Milstein said that, in addition to the therapy, Mohr was also taking Humira, an arthritis drug that works by blocking tumor necrosis factor alpha or TNF, a protein that stimulates arthritic inflammation. Humira blocks TNF production by suppressing the immune system.
Okay, first off, Humira does not block TNF production nby suppressing the immune system. Humira is a humanized form of Remicaide, and both are ANTIBODIES to TNF. An antibody binds to the soluble TNF in the blood stream and prevents it from activating other cells. A portion of the Remicaide molecule is derived from a mouse antibody. The Humira version has been fully humanized in order to decrease the number of infusion reactions --- which is like a cross between anaphylatic shock and what would happen if you got the wrong blood type. Treatable, but VERY serious and generally precludes you from getting that treatment (or any of the others in the family) again.
However, one of the obstacles to gene therapy is limiting activity to a single spot.
Umm, NO. Let me state this very simply, the NIH and the FDA are not going to allow human clinical trials with any virus that can proliferate out of control. There's nothing in the original article that suggests that they found the viral vehicle from the therapy through out the patient's blood stream (not that this isn't possible, but I'm saying it's very unlikely. But I can't say for certain without knowing the exact virus and what had been done to it).
Histoplasmosis infection is a documented side effect ofHumira, but is rarely fatal.
1) They do not know when the patient contracted histoplasmosis.
2) If it spreads beyond the lungs, it is very life threatening.
3) For anyone under immune-suppression, histoplasmosis is very dangerous because it is very easy to spread through the body.
4) Humira suppresses the immune system by soaking up the TNF --- without TNF, it is very hard for your body to start an immune response.
5) According to the WP: "[the patient] was also taking conventional immune-suppressing drugs for her arthritis". Let's see, I'm betting at the least she was taking prednisone. Possibly methotrexate (a chemotherapeutic used for treatment of autoimmune diseases). Either of these alone would have left her vulnerable to infection, add humira, and well...
Now I can hear someone asking, "Well, they shouldn't have let her participate if she was on those drugs". Wrong. First, it's is unethical to withdraw treatment that is controlling a disease to test another treatment. I'm guessing that they were using the experimental therapy on a joint that was continuing to be affected despite her treatment in the hope of maintaining her mobility. Plus, the question is Will the new therapy aid her more than her current regimen. ie, will the addition of this treatment make her even better? The next thing would be to see if this treatment alone could help patients with less severe forms or fewer years of the disease.
The only possible short-sightedness of the protocol is that they should have been monitoring her monthly for opportunistic infections like histoplasmosis, especially given the fact that the fungus is endemic to the area she lives in. But they may have been doing that already, or the test may be less than perfect.
Inexplicably, Mohr suddenly became ill in July even though she had beentaking that drug for years and the fungus that causes histoplasmosis isubiquitous in the area where she lived.
Okay, here's the deal, histoplasmosis is like tuberculosis -- it can lie dormant in the body. We can't say for certain why these organisms reactivate when they do -- Blockers of TNF do contribute because TNF helps cause and maintain the granulomas that wall the bacteria/fungi off from the body. But it isn't unheard of for someone to be fine on immunosuppressants for some number of years before having a reactivation.
I talked about this to Hildegund Ertl, a University of Pennsylvania gene therapy expert. She pointed out that it takes about two and a half weeks before a gene therapy becomes fully effective, making it unlikely that Mrs. Mohr's immediate post-injection vomiting was caused by the therapy, even if it did get out of control in other parts of her body.
However -- and this is my interpretation, not Ertl's -- the therapy could, as it took effect, combined with Humira's effects to cause a progressive shutdown of Jolee Mohr's immune system -- and worsening of the disease -- beyond what would have been seen with Humira alone.
1) AGain, willing ignorance of the fact that the patient was on other immunosuppressants.
2) I would like to know the timing of the patient's last Humira injection to comment more on the timing. If the author is getting this just from newspaper articles, they don't know that either.
3) Ertl (declaration: I know this professor in passing, though I doubt she remembers me) is absolutely correct. Virus, like bacteria and cells for that matter, have a set amount of "doubling" time. Most viruses used for gene therapy are also not completely competent to reproduce and are even slower. The post-injection vomiting could not be caused by the therapy -- unless something really screwy went on and the therapy went into an artery or something. Coincidence, really.
That Mohr was given the injection in spite of her fever and signs ofinfection was a mistake.
I thought I should note when I actually agreed with the author. However, I can understand the clinician's POV --- low grade fever is often a sign of an autoimmune flare. He probably thought that he/she was helping the patient possibly. However, I don't know the standard operating procedures of the trial or anything. But more tests should have been run before the drug was administered.
Most gene therapy trials are for serious diseases. Only a few, like the Targeted Genetics trial for arthritis, involve mild or moderate conditions that can be treated by other drugs. But until the therapies are better understood, even these few trials are too many.
"Why in the world would you do gene therapy for mild rheumatoid arthritis which is controlled by existing drugs out there?" asked Milstein. "They'd been working great for her. She was tolerating the drugs, responding well to them, and certainly was able to live an active, healthy life."
OMG --- this makes me really question the qualifications of the author -- what science/medical training do they have? Do they know anyone with an autoimmune disease?? Rheumatoid arthritis is a progressive destructive disease that leaves many patients unable to walk without severe pain due to damage to foot and ankle joints, as well as the knees and hips. Not to mention the increased risks for atherosclerosis. Plus, treatments like prednisone increase the risks for stroke and type II diabetes. Stress and infections tend to trigger even more flares making patients captives in their own homes during flu seasons or large gatherings for fear of getting sick. Anyone who knows someone with an autoimmune disease would never say that they are not "serious diseases". And the existing drugs don't work that great, really. Plus, the pain relievers that did help for many -- celebrex etc -- have been removed from the market due to the risk of stroke. I get the lawyer is grandstanding and trying to put on a good face for the lawsuit, but give me a break. The patient probably was starting to face actual constraints in her daily life and had hoped that the trial would really help her and possibly enable her to cut back on some of the medicines she was taking.
Okay, rant over.