Generic medications used frequently in the management of heart disease patients also have the potential to bolster the immune systems of patients with Ebola virus and some other life-threatening illnesses, researchers report this week in mBio®, the online open-access journal of the American Society for Microbiology.
Unlike other medications in development for Ebola, which attack the virus, statins and angiotensin receptor blockers typically used for heart disease work on the host response, or a person's biological reaction to the virus, said lead study author David S. Fedson, MD, a retired professor of medicine at the University of Virginia and expert on influenza and pneumococcal vaccination, and pandemic preparedness. Specifically, the drugs stabilize or restore the integrity of endothelial cells lining the blood vessels. Endothelial cell dysfunction has been a central feature of human Ebola virus disease, he said, leading to severe fluid and mineral losses.
"This approach to Ebola treatment has two advantages," Dr. Fedson said. "First, it uses inexpensive generic drugs that are widely available in any country with a basic healthcare system, and most physicians who treat patients with cardiovascular diseases are familiar with these medications. Second, because this strategy targets the host response to infection, these drugs might be used to treat patients with any form of acute infectious disease in which a failure to overcome endothelial dysfunction could lead to multi-organ failure and death."
The statin/angiotensin receptor blocker combination was found to help improve survival in 100 Ebola patients treated in Sierra Leone, Dr. Fedson said. In a pilot study last fall, patients were given the drugs atorvastatin (40 mg/day) and irbesartan (150 mg/day) at several hospitals in West Africa. While study reports were not published, Dr. Fedson said, reports indicate that rapid clinical improvement was seen in almost all patients. Only two are known to have died: one was critically ill when first seen and died soon after; the other initially responded to three days of combination treatment but relapsed and died when combination treatment was stopped and he was instead given an antiviral agent. The study results need to be replicated, Dr. Fedson said.
When pandemics hit, "you have to have something that ordinary doctors in ordinary countries can use to treat ordinary patients," he said. "We have extraordinary medicines that cardiovascular scientists have developed which modify not just endothelial function but all kinds of things that are part of the host response to infectious disease. In combination they work even better than they do alone."
Treating the host response would not prevent or cure Ebola virus infection itself, Dr. Fedson said, "but it could allow individual patients to survive long enough to develop an immune response that eliminates the virus. These agents could be used in combination with antivirals if they are available."
To move forward, researchers should consider four courses of action, Dr. Fedson said: undertake research on the host response to Ebola virus infection, including involving scientists who understand endothelial cell biology; perform clinical studies in West Africa to test statin and angiotensin receptor blocker combination treatment in Ebola patients; incorporate any successful treatment of the host response in other clinical trials of interventions against Ebola; and recognize the implications of treating the host response for other diseases.
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