Saturday, May 29, 2010

New Experimental Treatment for Ebola Zaire Shows Promising Effect in Monkeys

Scientists from the Boston University School of Medicine in collaboration with USAMRIID have developed a novel treatment for Ebola Zaire that has shown promising results and potential for treatment of humans exposed to the virus.
The study published in the Lancet titled "Postexposure protection of non-human primates against a lethal Ebola virus challenge with RNA interference: a proof-of-concept study" is a major step forward in treating Ebola exposure.

Ebola Zaire has the highest mortality rates of all the Ebola viruses at approximately 83% for all recorded epidemics.

Using small interfering RNAs (siRNAs), the authors targeted the L protein, VP24, and VP35. The L protein is the viral polymerase, and is also responsible for capping and polyadenylation of newly synthesized viral proteins making a functional L protein required for Ebola virus replication. VP24 and VP35 have both been identified as inhibitors of IFN-alpha/beta production and IFN-alpha/beta and gamma signaling. The ability of the Ebola virus to interfere with IFN production and signaling allows it to escape host immunity.

Lipid nanoparticles (LNPs) are the most widely used siRNA delivery approach. In this study, the research team used a proprietary technology called SNALP, or stable nucleic acid-lipid particles, to deliver the therapeutics to disease sites in animal models infected with Ebola Zaire.

Two test groups were established. The first group of three rhesus macaques was given anti-Ebola Zaire siRNAs intravenously, 30 minutes after exposure to the virus, and again on days 1, 3, and 5 post exposure. A second group of four macaques was given the treatment after 30 minutes, and on days 1, 2, 3, 4, 5, and 6, after challenge with Ebola Zaire.

Two of the three animals in the first group (30 min, days 1, 3, 5) were protected from Ebola and survived. All four of the monkeys given treatments (30 min, days 1, 2, 3, 4, 5, 6) survived. The only side effects observed in either study were elevated liver enzymes which could have been an artifact from the viral infection itself.

This study represents the first demonstration of complete protection against a lethal human infectious disease in nonhuman primates using RNAi, according to lead author Dr. Thomas W. Geisbert of the Boston University School of Medicine. Dr. Thomas Geisbert and his wife Joan are highly revered experts in the Bio Safety Level-3 (BSL-3) and BSL-4 world doing research on Ebola, Marburg, and others.

Geisbert believes their work justifies the immediate development of Ebola SNALP as a countermeasure to treat Ebola infected patients, either in outbreaks or accidental laboratory exposures. Obviously, clinical trials are difficult in any situation involving a life threatening virus so in order for this to be tested, an outbreak will have to occur. It will be interesting if this therapy will ever be used in the field, and if that opportunity presents itself, how effective it will be in humans.

Ebola virus exists as 5 strains and causes hemorrhagic fever (Reston and Tai, only in monkeys). The virus, which can be infectious by aerosol, but far more contagious via blood and body fluids, is of concern both as a global health threat and a potential agent of biological warfare.

Currently there are no available vaccines or therapies for Ebola, therefore researchers working with the virus have to observe maximum containment (BSL-4) rules. BSL-4 personnel wear positive pressure "space suits" breathing filtered air as they work, and all laboratory waste streams are sterilized.

The SNALP-RNAi therapeutic used in the study was developed by Tekmira Pharmaceuticals Corporation of Vancouver, BC. Previous research showed that these siRNAs completely protected guinea pigs when administered shortly after a lethal dose of Ebola Zaire was administered. Further studies in monkeys will be necessary to refine dosing, toxicology and other issued before the treatment could be licensed for human use.

"The significance of this report goes beyond the protection against Ebola virus," said COL John P. Skvorak, commander of USAMRIID. "It also represents the potential for this concept to be applied to other viral infections."

On a personal note, I am very excited about the potential for this treatment to be successful. I have always been interested in doing more "exotic" viral research and knowing there is a treatment potentially available is a major step forward for treating outbreak victims.

Lance D. Presser has a PhD in Microbiology & Immunology, and is a Public Health Laboratorian.

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