An experimental drug that protected monkeys from the deadly Marburg virus appears to have potential for treating people who have been exposed to the virus, according to a study published in the July 23 edition of The New England Journal of Medicine. Marburg virus is closely related to Ebola virus and also causes a severe hemorrhagic fever.
The research was jointly conducted by the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) and the biotechnology firm Sarepta Therapeutics, Inc., using a compound known as AVI-7288.
Taken together, the results of efficacy testing conducted in nonhuman primates and safety testing performed in a Phase I clinical trial suggest that AVI-7288 has the potential to be used to treat Marburg virus infection in humans when administered post-exposure, according to the authors.
Case fatality rates associated with Marburg virus have been reported to be nearly 90 percent and the virus is deemed a potential “Category A” bioterrorism agent by the Centers for Disease Control and Prevention. No licensed vaccine or therapy is currently available for Marburg virus infection.
For over a decade, USAMRIID and Sarepta have been collaborating to develop and test a class of antisense compounds known as phosphorodiamidate morpholino oligomers (or PMOs), according to senior author and USAMRIID Science Director Sina Bavari, Ph.D.
Antisense drugs are designed to enter cells and eliminate viruses by preventing their replication, Bavari explained. The drugs act by blocking the translation of critical viral genetic sequences, preventing a key viral protein from being made and giving the infected host time to mount an immune response and clear the virus. AVI-7288 specifically targets the viral messenger RNA that encodes Marburg virus nucleoprotein.
Led by Bavari and Travis Warren, Ph.D., the USAMRIID team performed a series of studies involving a lethal challenge with Marburg virus in nonhuman primates to determine the efficacious dose and regimen of AVI-7288, as well as to characterize the drug exposures in animals that produced efficacy. Cynomolgus macaques were exposed to Marburg virus and then received one of three treatments: AVI-7288, an inactive placebo, or a saline control.
Survival in infected nonhuman primates was dose-dependent, with survival rates of 0%, 30%, 59%, 87%, 100%, and 100% among monkeys treated with AVI-7288 at a dose of 0 mg, 3.75 mg, 7.5 mg, 15 mg, 20 mg, and 30 mg per kilogram of body weight, respectively. In contrast, none of the monkeys treated with placebo or the saline control survived.
Read the rest of the USAMRIID news release HERE