The prospect of a influenza pandemic has concentrated the minds of vaccine makers. There has been a lot of new research and development on newer, faster and cheaper ways to make flu vaccines. The antiviral field hasn't been quite as active, although now things seem to be picking up. Until now the antivirals (all four of them!) have been in two main classes, the old M2 inhibitors (adamantanes) and the newer neuraminidase inhibitors (oseltamivir, zanamivir; and waiting in the wings, peramivir). Now we are hearing about new drug targets:
One of the promising things about the work is that the drugs and drug targets that are in the pipeline would diversify the number of classes of flu drugs if they are successfully brought to market. That, in turn, would lower the risk posed by drug resistance.[snip]
Later this week, scientists will present an update on work to bring to market a new drug, provisionally called T705, which targets the polymerase protein. [Dr. Frederick Hayden of WHO] said Phase 2 clinical trials will begin in Japan later this year.
[snip]
Dr. Robert Krug, of the Institute for Cellular and Molecular Biology at the University of Texas at Austin, reported on finding a drug target on the non-structural protein of the virus. A drug target is a site on a protein created by the virus that could be neutralized by the right chemical molecule.
Krug reported that his lab had screened molecules that might be used against the target, and have come up with a good "hit." But he cautioned that even if the work goes well, it could be five years before a drug could be developed, tested and marketed.
The non-structural or NS1 protein of influenza makes an attractive target for a drug because it does not change from virus to virus, unlike other parts of flu viruses. (Helen Branswell, Canadian Press)
New classes of drugs mean there are more options if a virus manages to escape by developing resistance. They also may work better or be useful in combination with a drug using another mechanism. It could also be that none of the new drugs will be of any help in managing or slowing a pandemic but still find an important use in treating individual cases.
While we are talking about new drugs, however, it is somewhat disappointing not to see more information on the utility of a class of old drugs, the statins (see here, here and here). Statins are cheap, plentiful and have a fairly good safety profile.
The statins are used for their cholesterol lowering feature but seem to have other effects as well. Now a paper on another cholesterol lowering drug, gemfibrozil, is also showing an ability to protect against the lethal effects of influenza infection (Budd et al., Antimicrob Agents Chemother. 2007 Jun 11). Survival against H2N2 in mice increased from 26% to 52% after an intraperitoneal injection of gemfibrozil 4 to 10 days after intranasal inoculation with the virus. Maybe we should be looking at the cholesterol connection a little closer?
The new drugs under development will have to go through an intense process of safety and efficacy testing. Meanwhile we also have drugs like the statins and gemfibrozil that are available and approved and could be brought into service immediately in the event of a pandemic. No big bucks here. These are drugs off patent and not hugely profitable.
But wouldn't it be useful to be investigating their utility a little more avidly? Or am I missing something?
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Tangential question: if statins improve the chances of surviving the ravages of influenza, do people with lower cholesterol numbers have any better ability to do so?
I understand that it may well be unrelated. The second part of the question: if having a Rx for a statin drug means you have better coverage in case of a flu pandemic, are people with lower cholesterol numbers (and no Rx) at a disadvantage?
wenchacha: No one knows the answers to your (good) questions. Here are the possibilities. (1) statins aren't useful at all for influenza; (2) they are useful because they lower cholesterol, which has some connection to the cytokine dysregulation; (3) they are useful because they have another pharmacologic effect not connected with cholesterol. You can see that if we knew which of these were true we would also know something about your questions. My concern is that there doesn't seem to be enough work going on about answering these questions. Maybe I just don't know about it. There is undoubtedly some work but is it enough commensurate with the possible pay-off?
Anoter tangential question.
Is anyone stockpiling drugs for the treatment of secondary infections? Figures on the numbers of deaths due to seasonal flu seem to vary depending on how you count cause of death - much like AIDs - but secondary pneumonia etc. could be a major contributor and I have not seen evidence that plans are stockpiling for such. Has anyone information?
While we are talking about new drugs, however, it is somewhat disappointing not to see more information on the utility of a class of old drugs,..
How about no drugs? I get the flu, maybe 1 or 2 times/year for the past 40 years. Never taken a flu vaccine or a drug. (Maybe, a little Nyquil every now and then). You get sick, you rest, you get over it.
The immune system is a heluva lot smarter, more advanced and more efficient than the drug maker or public health guru.
While jumping around the web I ran across an interesting article. Argue it if you will, I support it.
New Scientist has an article: Cannabis compound reduces skin allergies in mice. Now wait before you jump to conclusions, read the information below.
A study on mice found that the immuno-suppressive properties of THC (the main psychoactive compound in cannabis) was an excellent remedy for allergenic skin rashes.
Apparently mice administered THC produced fewer cytokines too.
The key word above is "fewer cytokines".
In a bird flu pandemic with little medical care available, perhaps those under 40 could do worse than ingesting a hash cake or two?
Last sentence says: Researchers stress that people who currently suffer from autoimmune disease should not try to self-medicate with marijuana because of its side-effects.
I'll take the "side-effects", thank you.
http://www.newscientist.com/article.ns?id=dn12016&feedId=online-news_rs…
.......
Lea. I think you have hit on the perfect preventative for a pandemic. Even if it doesn't work...you won't care anyways.
ps. I have been waiting for the alcohol lobby herd of epidemiologists to weigh in...a couple of drinks (or more) a day will prevent the cytokine storm.
/:0)
Lea: I won't argue this on influenza grounds. I think it is a pretty weak reed to lean on as a treatment or preventive for pandemic flu (although as Tom sagely observes, it could improve your attitude toward it). I support legalization of cannabis because it makes sense not to criminalize it.
Thanks Tom DVM, do enjoy reading what you write in this blog, keep it up please.
revere, ditto on the legalization of cannabis. Off topic a tad; let's be compassionate enough as a society to not put people in prison or jail anymore for a Non-violent "crime".
If a cannabis connoisseur survives this pandemic I hope they have tons of seeds stashed.
There will be a paper on statins Friday at the Options Conf. It's still under embargo.
Thanks for the heads up, Maryn. Posting on a piece of yours tomorrow a.m.
Revere, whats the availability of these old drugs as opposed to new? If they worked (?) would or could they ramp up production to cover the world. I see Roche this morning produced yet another study saying that using Tamiflu propylactically would cut the deaths in half if panflu arrives.
Gave mice gemfibrozil after "4 to 10 days"?
If they had used H5N1, the mice'd have been pushing up quite a few daisies by then.
crfullmoon
Perhaps, but IIRC, previous research on statins has suggested that any protective effect against influenza takes weeks to come into effect. So if you came down with H5N1 or any panflu, starting statins then would do you little good. Even assuming a benefit were confirmed, it might only help those already taking statins for cholesterol.
On the other hand, an injectable drug that lowered mortality rates when given after infection could theoretically help people after they got sick. (The usual caveats about the availability of care aside.)
"There will be a paper on statins Friday at the Options Conf. It's still under embargo."
Any further news? Can it be accessed?
http://newfluwiki2.com/showDiary.do?diaryId=1130
The statins paper turned out to be some very preliminary data by the UK's Health Protection Agency, drawn from a lookback at medical records in the Royal College of General Practitioners's sentinel surveillance database. Net result: Among known users of statins, a modest protective effect (slight decrease in odds ratio) against acute upper respiratory infection, but only among those who had already been vaccinated against flu; no visible protective effect for ILI or bronchopneumonia or among the not-vaccinated. They are going to be adding more records to the mix and trying to stratify the data several different ways, by time of year and by seriousness of seasons. Obviously at this point there are a lot of potential confounders. The abstract is not online as far as I know.