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 Steps towards fighting Ebola virus infographic
Graphic shows how Ebola affects vctims and explains how advances in gene silencing could offer a post-infection cure.
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MEDICAL

Steps towards fighting Ebola virus

By Duncan Mil

August 1, 2014 - The Ebola virus hijacks human cells to inject its genome and turn the cells into virus factories. Recent advances in molecular biology suggest that gene-silencing drugs could block this process.

Ebola emerged in 1976 in two simultaneous outbreaks in Zaire and Sudan. The virus disables the immune system, causes massive bleeding, diarrhoea and fever, leading to organ failure and then death.

The Zaire species of Ebola virus (ZEBOV) is the most virulent strain of the haemorrhagic fever -- up to 90 percent of infected people die during outbreaks, making Ebola one of the most feared diseases known to man.

The current Ebola outbreak is the worst the world has ever seen. It has jumped borders from Guinea to Sierra Leone to Liberia, raising fears of catastrophic world consequences if allowed to spread.

There is hope, however. Of the five distinct species of Ebola, the four found in Central Africa are fatal to humans. The Reston strain, found in China and the Philippines, appears to be benign. Genetic analysis of the strain causing the West African outbreak indicates that it is closely related to ZEBOV but is less fatal, with a 60 percent death rate.

There is also hope from the medicine men. Since the virus first appeared, people have been searching for ways to prevent or treat Ebola infections. Now, at the University of Texas Medical Branch, Professor Thomas Geisbert and his team, working in full-body plastic “spacesuits” within laboratories known as “Hot Zones”, have had successful results in animal studies.

In 2010 the Lancet published research by Geisbert and his wife Joan, working in collaboration with Canadian-based biotech company Tekmira and the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID). Their studies were carried out in Chinese rhesus macaques infected with a lethal dose of the deadly ZEBOV.

They used synthetic versions of viral nucleic acid, so-called “small interfering RNA”, or siRNA, a type of molecule that can block particular viral genes -- the codes the virus needs to make proteins to survive. The cocktail targeted three Ebola genes -- L polymerase, VP40 and VP24 -- viral proteins which kick-start replication, or are involved in “budding” or releasing new virions from a host cell, and disabling an infected host’s immune system.

The trial used Lipid Nanoparticle (LNP) delivery technology developed by Tekmira. Basically the siRNA drug was packed inside fat molecules which, when injected, travel through the bloodstream to target tissues.

Ten days after treatment, researchers were unable to detect the virus at all in monkeys that had received daily doses of the cocktail. “The siRNAs inhibited the replication of the virus and completely protected the monkeys against death from haemorrhagic fever”, Geisbert told National Geographic News. “This has never been done before”.

Having shown a treatment that is effective in animals, the next stage would be to carry out toxicity tests in animals and metabolic tests in man to see how the body tolerates the drug. Then, and only then, would permission be given to carry out clinical trials to see whether the drug is effective clinically.

In January 2014, Tekmira commenced a Phase I clinical trial using TKM-Ebola, and in March it was granted a Fast Track designation from the U.S. Food and Drug Administration (FDA). However, this trial was stopped because of side-effects at the highest dosage.

As the death toll in west Africa passes 730, including 60 medical personnel, and fears mount that the outbreak could spread to other continents, there is debate and frustration as to what side-effects would be acceptable when testing new treatments in a situation like this. Says Geisbert: “None of us, certainly, want to have something that we develop cause problems in humans. So it’s just a difficult situation”.
/ENDS

Sources: CDC, National Institute of Allergy and Infectious Diseases at the National Institutes of Health, University of Texas Medical Branch, WHO, National Geographic

Sources
PUBLISHED: 04/08/2014; STORY: Duncan Mil
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