Tuesday, August 11, 2015

mBio Letter: Statins Suggested As Possible Treatment For MERS


Photo Credit WHO


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Over the past decade we’ve seen statins proposed as a potential treatments for an often deadly side effect seen in severe flu called a `cytokine storm’, and while the jury is still out on their effectiveness (we’ve seen very few studies, and mixed results), there is a certain elegance to the theory behind their use.


Cytokines are a category of signaling molecules that are used extensively in cellular communication. They are released by immune cells that have encountered a pathogen, and are designed to alert and activate other immune cells to join in the fight against the invading pathogen.


This cascade of immune cells rushing to the infection can - if it races out of control - literally kill the patient. Their lungs can fill with fluid (which makes a terrific medium for a bacterial co-infection), and cells in the lungs (Type 1 & Type II Pneumocytes) can sustain severe damage.


Statins have an anti-inflammatory effect, and theoretically should help dampen down this runaway cytokine storm, and are one of several immunomodulatory treatment strategies under review.


Dr. David Fedson – former Professor of Medicine at the University of Virginia School of Medicine and formerly Director of Medical Affairs, Aventis Pasteur MSD - has long championed the idea that we should be looking at relatively cheap, easy to produce statins for pandemic flu, which he believes may help modulate the immune response (see Dr. David Fedson: The Case For Using Statins In A Pandemic).

The problem is, while some studies on statins and pneumonia have yielded promising results, not all of the research is in agreement. Complicating matters, since many statins are now generic, there is little financial incentive for drug companies to fund expensive research.  A few earlier blogs on the subject include:


Study: Statins, Influenza, & Mortality

Another Study On Statins And Pneumonia

Statins Revisited


Unlike with novel influenza – which can sometimes be successfully treated with antivirals like oseltamivir (Tamiflu ®) -  there is currently no established treatment (beyond supportive care) for MERS cases.  Convalescent serum is under review, but even if that proves successful, it would not be widely available during a major outbreak.  


With a mortality rate (among those sick enough to be hospitalized) near 40%, and the possibility of seeing larger outbreaks in the future, there is a genuine need for some kind of pharmaceutical treatment option. Even if it only reduced mortality rates.


Today the journal mBio carries a letter recommending statins be looked at as a possible treatment for MERS-CoV infection.  The author outlines his rationale (which you can read by following the link) in some depth, but I’ve only excerpted his opening and closing paragraphs. 


Statins May Decrease the Fatality Rate of Middle East Respiratory Syndrome Infection

Shu Yuan


The recent paper by Totura and colleagues (1) revealed that Toll-like receptor 3 (TLR3) signaling contributes to a protective innate immune response to severe acute respiratory syndrome coronavirus (SARS-CoV) infection. Despite the importance of SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV) as public health threats, there are currently no drugs available to treat these coronaviruses, with current evidence suggesting that the antiviral drugs ribavirin and interferon (IFN) are only slightly efficacious in ameliorating SARS-CoV or MERS-CoV infections (2). Now human-to-human infections of MERS-CoV are more frequently reported, with a total case fatality rate of 37.7% (2). Therefore, a feasible but effective treatment is needed urgently, especially treatment with FDA-approved drugs, including some over-the-counter (OTC) drugs.


Among TLR-MYD88 antagonists, statins are the most common FDA-approved drugs (atorvastatin will be sold as an OTC drug). Statins do not affect the MYD88 level significantly under normal conditions but maintain (stabilized) MYD88 at the normal level during hypoxia or after hydrogen peroxide treatments (8, 9). Furthermore, atorvastatin at 10 µM significantly attenuated NF-κB activation within 24 h, whereas at lower doses of 0.1 and 1 µM, the treatment time had to be prolonged for up to 48 h for a significant inhibition to occur (10). Thus, an early and high dose of a statin (such as a single dose of 40 mg atorvastatin per day, equaling a 0.1 µM plasma concentration) might be an idea for treatment of MERS-CoV infections. Given that 3- to 10-times-higher levels of inflammatory cytokines and chemokines were observed after MERS-CoV infection than after no infection (3), statins may not be very effective for late-stage patients. Timely administration of statins may be crucial to surviving MERS-CoV infection.


Once again, the theory behind its use seems reasonable, but we’ll have to wait for real-world results before we know whether statins are really an effective treatment option for MERS.