Tuesday, October 07, 2014

Investigational Antiviral Drug approved for use on US Ebola patient

The FDA approved the use of an investigational drug, CMX001 (brincidofovir),  to attempt to treat Ebola Virus Disease in the sole US case so far.  The drug has been in clinical trials for Cytomegalovirus (CMV) infection, a common complication in bone-marrow transplants and other immunosupressed populations.  The drug has also been used for Adenovirus infections in pediatric cancer patients.  Based on its activity against poxviruses it was selected for investigation as a possible treatment for Smallpox (Variola) infection for bioterrorism defense.

Brincidofovir is an orally active prodrug of cidofovir (Vistide), an injectable antiviral drug used to treat CMV retinitis in AIDS patients.  Brincidofovir is converted to the active drug in the body and its lipid conjugation allows lower plasma levels (less toxicity) and higher levels inside cells, where it can act on the virus.

Link to Publication of CMX001 efficacy in Herpes Virus Infections -Note: CMV is in the Herpes Virus family.  Paper give some background on the mechanism of action in Brincidofovir.

Chimerix Press Release

Thursday, October 02, 2014

Ebola and Melatonin: Could a Common Sleep Aid help fight Ebola?

The growing outbreak of Ebola Virus Disease in West Africa has focused the world's attention on one of the most deadly infectious diseases known. Rapid depletion of experimental drugs including those used to successfully treat several American patients have clinicians scrambling for something other than supportive care.  

A recent paper describes the possible use of melatonin, a natural hormone that controls the wake-sleep cycle and widely available sleep aid, to counter some of EVD's severe effects on the body.  Because of Melatonin's wide availability and excellent safety profile, a positive effect could be an important weapon in the fight against the outbreak in Africa and a potential addition to the treatment of EVD.  Because Melatonin is classified as a food additive in the US,  it can be purchased over the counter and is relatively inexpensive. Obviously more work needs to be done in clinical trials, which could begin immediately since the human safety phases of a clinical trial can be skipped, because of its widespread use. 

Ebola kills in a particular way that turns the body's immune system on itself.  Ebola virus infection causes a cascade of immuno-inflamatory reactions including the production of reactive molecules that damage the lining of blood vessels and trigger the clotting cascade in the blood. This reaction has similarities to bacterial sepsis.  Several studies have shown a positive effect from Melatonin in preventing both endothelial damage and intravascular coagulation.  The author's of this paper have suggested that because similar mechanisms are at work in Ebola virus infection, Melatonin may be beneficial in treating EVD.

Link to article: 

Ebola virus disease: Potential use of melatonin as a treatment
Dun-Xian Tan, Russel J. Reiter and Lucien C. Manchester
Accepted manuscript online: 27 SEP 2014 01:25AM EST