Marburg shares the same virus family as the four species of its more active sibling, Ebola. These filoviruses are rare, originating from isolated fruit bat colonies in remote central Africa. However, the results of infection in primates, including humans are devastating and terminal.
In ongoing attempts to find a treatment and cure for the lethal Marburg filovirus, the US Army Medical Research Institute of Infectious Diseases (USAMRIID) has joined forces with Washington-based AVI BioPharma, Inc to research the effects of gene silencing on the viruses using synthetic RNA nucleotides. A preclinical trial with rhesus monkeys using siRNA technology has brought a most promising outcome in the search for a cure.
Marburg and Ebola Hemorrhagic Fevers
In the world of hemorrhagic fever viruses, Marburg and Ebola are particularly unforgiving and destructive. Within 1-4 days of exposure, Marburg symptoms begin with a high fever, severe headache and profound fatigue. At 5-7 days, most victims develop lesions on their skin, liver and spleen and some begin to hemorrhage and experience organ failure. Bleeding sometimes occurs from the GI tract but can also occur into the lungs and pericardial space, from the eyes and even sweat glands. Most deaths occur within 20 days and are due to massive hemorrhage and organ death.
Filoviruses are transmitted by contact with body fluids or the handling of infected or dead people or monkeys. Health workers are at high risk when caring for victims but following strict precaution guidelines, proper disinfection techniques and patient isolation protocols greatly reduces it. It is also possible to aerosolize the viruses as has been shown in weapons studies.
This family of virus uses negative sense RNA as its genetic replication tactic. Antisense technology attempts to block the viral RNA expression and thereby stop replication and the spread of the virus.
AVI BioPharma and the USAMRIID
The US Department of Defense supports and funds the USAMRIID in disease and biological threat research for the purpose of protection of soldiers at war. Marburg and other hemorrhagic fever viruses have become a theoretical source of biological weapon material for terrorists.
As far back as April of 1988, Russian scientist Dr Nikolai Ustinov became infected by needle stick while injecting the virus into guinea pigs. He was dead by the end of the month. The virus taken from his body was stronger than usual, and was kept alive for research and named, "Variant U" in his honor. Within two years, the Soviet Union successfully developed a highly effective biological weapon by placing aeresolized Variant U into a warhead.
Aeresolized Marburg virus proved highly infective with very low amounts in closed spaces during tests on monkeys. In addition to the ability to distribute the virus in a bomb, Marburg and Ebola are both relatively easy to manipulate and to theoretically blend with other viruses such as smallpox in order to produce a stronger and much more highly contagious virus. Horrifying ideas like these are magnified by the actual horror and pain of the disease itself, which make it an ideal weapon of terror.
AVI released the most recent study results to Nature Magazine on August 23, 2010 displaying brilliant findings with use of morpholino oligomers in monkeys. Morpholino oligomers are a type of antisense nucleotide. Antisense nucleotides are synthetic strands of RNA that are designed to bind to preexisting sense RNA strands in order to inhibit their function of protein production and thereby stop viral replication.
siRNA Preclinical Study of Marburg and Ebola Virus
The study using AVI-6002 for Ebola virus and AVI-6003 for Marburg virus ended with strong evidence supporting their use in controlled post-exposure administration to subjects. When given within three days of exposure, the trial medications appear successful. According to the August 23,1010 AVI BioPharma website press release, “Treatment of Ebola virus-infected primates with AVI-6002 led to 60% survival, and treatment of Marburg-infected primates with AVI-6003 conferred 100% survival, compared to control groups where both viruses were universally lethal.”
Ongoing development will likely soon lead to human trials. Hopefully this will add treatment options for victims since supportive care alone usually ends in organ failure and death. Antisense research extends beyond filoviruses and encompasses other virus families too. Among these are the dengue fever virus and influenza. Gene silencing technology is showing significant progress towards the treatment of filoviruses and an ease of human suffering.
Sources:
Ali S Khan, Anthony Sanchez and Anne K Pflieger. "Filoviral haemorrhagic fevers".British Medical Bulletin 1998,54 (No 3) Accessed 24 August 2010
Thomas H Maugh II. “Drugs block Ebola, Marburg viruses in tests” LA Times. 23 August 2010. 20100823. Accessed 24 August 2010
World Health Organization.“Global Alert Response, Marburg Hemorrhagic Fever”, World Health Organization. Accessed 26 August 2010.
Heather Ozmun - Heather Ozmun moved from her native city of San Diego, California to Austin, Texas in 1998 where she began a career as a paramedic. After ...
Join the Conversation