Friday, January 18, 2008

First Statins, Now Fibrates


# 1496



The idea of using cholesterol lowering drugs, called statins, to combat pandemic flu has been around for some time.  First championed by Dr. David Fedson, I've written on this on several times, the first time back in June of 2006.


In his paper on the subject, Dr. Fedson wrote:


Pandemic Influenza: A Potential Role for Statins in Treatment and Prophylaxis

David S. Fedsona

The next influenza pandemic may be imminent. Because antiviral agents and vaccines will be unavailable to people in most countries, we need to determine whether other agents could offer clinical benefits. Influenza is associated with an increase in acute cardiovascular diseases, and influenza viruses induce proinflammatory cytokines.


Statins are cardioprotective and have anti-inflammatory and immunomodulatory effects, and they thus might benefit patients with influenza.


This hypothesis should be evaluated by using administrative databases to search for reduced rates of hospitalization and death due to influenza‐related conditions among people taking statins.


These studies should be followed by laboratory studies of statins in animal and cell‐based models of influenza virus infection and, later, by clinical trials. Positive results from such studies would provide physicians in all countries with something to offer patients for treatment and prophylaxis of pandemic influenza.


Generic statins will be widely distributed and inexpensive. They might be the only agents that could alter the course of a global pandemic.



An unproven theory, but a tantalizing one. Worthy of further investigation.


Now, Australian researchers have studied a different class of cholesterol lowering drugs, called Fibrates, and believe they may also be beneficial in the treatment of pandemic influenza. 


Fair warning:  This is preliminary data, based on tests on mice, and more study is needed.


This excerpted from The Australian.



Tests home in on new hope against bird flu

Julia Hinde | January 19, 2008


Now a group of Australian researchers has published data that might point the way to an alternative - and potentially cheaper - way to fight the next major outbreak.


Led by Ian Clark of the Australian National University (ANU), the researchers used gemfibrozil, a drug already approved for human use as a cholesterol-lowering medication, to treat mice infected with a potent influenza virus.


The team reports a doubling in survival rates for infected mice when they were given a course of gemfibrozil, starting four days after they became infected.


According to ANU postdoctoral fellow Lisa Alleva, who is an author on the paper, gemfibrozil was chosen because as well as having cholesterol-lowering properties, it is known to have anti-inflammatory effects and reduces immune system particles called "proinflammatory cytokines".


Cytokines are important signalling molecules in the body which, during an immune response, signal immune cells to travel to the site of an infection.


But a number of recent studies have reported pronounced increases in proinflammatory cytokines after infection with potent influenza viruses. This has led many in the scientific community to suggest the high mortality associated with viruses such as avian flu might in fact be the result of a massive immune system overreaction - a so-called cytokine storm - which in turn triggers further inflammation, lung damage and even death.


Hence, the ANU team, rather than targeting the virus itself, set out to target the hypothesised immune system overreaction with an immune-modulating drug.


"We trawled through the literature believing that influenza mortality is primarily caused by an over-exuberant immune response," explains Alleva. "We looked for pre-existing drugs used in human populations that may have side effects which were anti-inflammatory.


"When we tried gemfibrozil, it worked so well, we ran with it."


In the paper - published in the journal Antimicrobial Agents and Chemotherapy (2007;51(8):2965-2968 - the researchers suggest that if this principle translates to patients, "a drug already approved for human use... might be adapted relatively fast for use against influenza, conceivably including human infection with a derivative of the avian H5N1 strain".



This is early research, and more work lies ahead. There were some caveats and limitations to this study:


  • The tests were done using the H2N2 influenza virus, not the H5N1 virus, which in Australia may only be done at CSIRO's Australian Animal Health Laboratory at Geelong.


  • These are also studies done on mice, which are not always predictive of how medicines will work on humans.


  • And the theory of the Cytokine Storm being a major contributor in the deaths of H5N1 patients, once the predominate theory, is now held in less high regard.   The jury is still out on that one.


These early results, while encouraging, are just a first step into determining the efficacy of using Fibrates to treat pandemic flu.


Anonymous said...

Why this is a dumb idea:

How long do you think it takes this drug to begin working effectively to reduce cytokine production?

Weeks to months. Far too late to treat infected patients - death occurs in days.

So, are the authors of these papers on statin and fibrate use advocating treating the entire populace with these drugs before infection?

With a pandemic wave lasting months to years, how many people would you be treating, hmmm?

FLA_MEDIC said...

I've seen it suggested in the past that you'd have to be on statins for 30 days before becoming ill for it to work.

Trouble is, no one has tested that hypothesis.

In this study, researchers claim a 50% reduction in mortality even when the Fibrates were started 4 days after infection.

Now, mice aren't the best test substitute for humans. I'd be a bit more impressed if they'd used ferrets.

This is an early study. We won't know if this approach has value until more work is done.

Goju said...

The NEJM report states that mice whose immune systems were depressed through drugs suffered the same mortality rate as those who were not treated.... indicating that the cytokine storm was NOT the key cause of death.