Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Novel 'antisense' therapies protect primates from lethal Ebola and Marburg viruses

23.08.2010
New studies show that treatments targeting specific viral genes protected monkeys infected with deadly Ebola or Marburg viruses. Furthermore, the animals were protected even when therapeutics were administered one hour after exposure—suggesting the approach holds promise for treating accidental infections in laboratory or hospital settings.

The research, which appears in today's online edition of the journal Nature Medicine, was conducted by the U.S. Army Medical Research Institute of Infectious Diseases in collaboration with AVI BioPharma, a Washington-based biotechnology firm.

Working with a class of compounds known as antisense phosphorodiamidate morpholino oligomers, or PMOs, scientists first performed a series of studies with mouse and guinea pig models of Ebola to screen various chemical variations. They arrived at a therapy known as AVI-6002, which demonstrated a survival rate of better than 90 percent in animals treated either pre- or post-exposure.

Encouraged by these results, the team conducted "proof of concept" studies in which 9 rhesus monkeys were challenged with lethal Ebola virus. Treatment was initiated 30-60 minutes after exposure to the virus. In these studies, 5 of 8 monkeys survived, while the remaining animal was untreated. Further experiments, including a multiple-dose evaluation, also yielded promising results, with 3 of 5 monkeys surviving in each of the AVI-6002 treatment groups when they received a dose of 40 mg per kg of body weight.

According to first author Travis K. Warren of USAMRIID, antisense drugs are useful against viral diseases because they are designed to enter cells and eliminate viruses by preventing their replication. The drugs act by blocking critical viral genetic sequences, essentially giving the infected host time to mount an immune response and clear the virus.

Ebola and Marburg cause hemorrhagic fever with case fatality rates as high as 90 percent in humans. The viruses, which are infectious by aerosol (although more commonly spread through blood and bodily fluids of infected patients), are of concern both as global health threats and as potential agents of biological warfare or terrorism. Currently there are no available vaccines or therapies. Research on both viruses is conducted in Biosafety Level 4, or maximum containment, laboratories, where investigators wear positive-pressure "space suits" and breathe filtered air as they work.

The USAMRIID team next turned its attention to Marburg virus, again screening various compounds in mice and guinea pigs to select a candidate for further testing. They settled upon AVI-6003, a drug that consistently conferred a high degree of efficacy (better than 90 percent survival) in both models.

Investigators conducted two pilot studies in cynomolgus monkeys to assess the efficacy of AVI-6003 against lethal challenge with Marburg virus. As with the Ebola studies, treatments were initiated 30-60 minutes after infection. All 13 animals receiving AVI-6003 survived. Additional research provided important information about the optimal therapeutic dose range of the compound, with a 40 mg per kg body weight dose protecting 100 percent of the monkeys following challenge.

"This report of successful early post-exposure treatment of filovirus hemorrhagic fever is significant on its own," said Colonel John P. Skvorak, USAMRIID commander, "but the drug characteristics of these PMOs also support investigation of potentially broader therapeutic applications."

Senior author Sina Bavari said USAMRIID has been collaborating with AVI BioPharma since 2004. In February of that year, an Institute scientist working in a Biosafety Level 4 laboratory stuck her thumb with a needle while treating Ebola-infected mice with antibodies. As a precaution, USAMRIID medical experts recommended the investigator be isolated for 21 days to ensure that she had not been infected.

Coincidentally, earlier that very day, Dr. Patrick Iversen from AVI BioPharma had presented a seminar at USAMRIID concerning the efficacy of novel antisense drugs against a range of viruses. When he found out that a USAMRIID scientist had potentially been exposed to Ebola virus, the company volunteered to design and synthesize compounds against the virus to treat her if the need arose.

The team at AVI worked for four straight days to generate human-grade anti-Ebola compounds. In the meantime, their regulatory staff worked with USAMRIID physicians to gain emergency approval from the U.S. Food and Drug Administration to use the compounds if necessary. Five days after the exposure, AVI delivered the compounds to USAMRIID's medical team.

Fortunately, the scientist had escaped infection with Ebola virus, so the compounds were never used. However, USAMRIID went on to test them in animal models, and has been collaborating with AVI ever since.

According to the authors, the investigational new drug applications (IND) for AVI-6002 and AVI-6003 have been submitted to the U.S. Food and Drug Administration, and they are now open to proceed with clinical trials.

Collaborating on the study were Travis K. Warren, Jay Wells, Kelly S. Donner, Sean A. Van Tongeren, Nicole L. Garza, Donald K. Nichols, Lian Dong, and Sina Bavari of USAMRIID; Kelly L. Warfield and Dana L. Swenson, formerly of USAMRIID; and Dan V. Mourich, Stacy Crumley, and Patrick L. Iversen of AVI BioPharma.

USAMRIID, located at Fort Detrick, Maryland, is the lead medical research laboratory for the U.S. Department of Defense Biological Defense Research Program, and plays a key role in national defense and in infectious disease research. The Institute's mission is to conduct basic and applied research on biological threats resulting in medical solutions (such as vaccines, drugs and diagnostics) to protect the warfighter. USAMRIID is a subordinate laboratory of the U.S. Army Medical Research and Materiel Command.

Reference:

Travis K. Warren, Kelly L. Warfield, Jay Wells, Dana L. Swenson, Kelly S. Donner, Sean A. Van Tongeren, Nicole L. Garza, Lian Dong, Dan V. Mourich, Stacy Crumley, Donald K. Nichols, Patrick L. Iversen and Sina Bavari; "Advanced antisense therapies for postexposure protection against lethal filovirus infections," Nature Medicine (22 August 2010).

Caree Vander Linden | EurekAlert!
Further information:
http://www.usamriid.army.mil

More articles from Studies and Analyses:

nachricht Antarctic Ice Sheet mass loss has increased
14.06.2018 | Technische Universität Dresden

nachricht WAKE-UP provides new treatment option for stroke patients | International study led by UKE
17.05.2018 | Universitätsklinikum Hamburg-Eppendorf

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

Im Focus: Photoexcited graphene puzzle solved

A boost for graphene-based light detectors

Light detection and control lies at the heart of many modern device applications, such as smartphone cameras. Using graphene as a light-sensitive material for...

Im Focus: Water is not the same as water

Water molecules exist in two different forms with almost identical physical properties. For the first time, researchers have succeeded in separating the two forms to show that they can exhibit different chemical reactivities. These results were reported by researchers from the University of Basel and their colleagues in Hamburg in the scientific journal Nature Communications.

From a chemical perspective, water is a molecule in which a single oxygen atom is linked to two hydrogen atoms. It is less well known that water exists in two...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

A sprinkle of platinum nanoparticles onto graphene makes brain probes more sensitive

15.06.2018 | Materials Sciences

100 % Organic Farming in Bhutan – a Realistic Target?

15.06.2018 | Ecology, The Environment and Conservation

Perovskite-silicon solar cell research collaboration hits 25.2% efficiency

15.06.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>