Syndicate content

Archive - Jun 23, 2009

Ebola Virus Infection Blocked in Cell Culture Experiments

Using existing drugs that block activation of either the PI3K pathway or the CAMK2 pathway in cells, researchers have shown that Ebola virus infection can be reduced or entirely blocked in cell culture experiments. This may represent an early first step toward the first successful therapy for this deadly virus. Ebola inflicts severe and often fatal hemorrhagic fever on its victims, producing 90 percent mortality rates in some outbreaks. No vaccine exists for the virus, and it is considered a high-risk agent for bioterrorism. Natural Ebola outbreaks strike periodically, often with devastating effect; recent examples include outbreaks in Uganda in 2008 and the Democratic Republic of the Congo in 2007. "The premise for this work is that the virus is essentially nothing without a cell," said Dr. Robert Davey, lead author of the current report. "It needs to rely on many cell proteins and factors for it to replicate. The idea is that if we can suppress the expression of those cell proteins for just a short time, we can then stop the disease in its tracks." The two key cellular pathways upon which Ebola, in part, depends were identified by a combination of siRNA-based screening and a newly developed algorithm designed especially to prioritize the results of siRNA screens. After initial experiments with artificially created, lab-safe Ebola “pseudotype” viruses (i.e., viruses with the Ebola coat, but with the genetic core from another virus) gave promising results, additional experiments were carried out with real Ebola virus in a maximum containment facility (BSL4). “With the real virus in the BSL4, we found that the PI3K inhibitor dropped virus titers by 65 percent, and if we used drugs which block CAMK2 function, it was just killed — stopped dead," Dr. Davey said.

Serum DNA Analysis May Identify Early Presence of Disease

A new study further confirms the potential diagnostic and prognostic utility of using circulating fragments of DNA to detect early-stage disease, according to researchers from Chronix Biomedical and collaborating institutions who reported their findings online on May 27 in Zoonoses and Public Health. The DNA fragments, referred to as serum DNA, are released into the blood stream in trace amounts during the disease process. Chronix Biomedical has developed proprietary technology that it says can find, isolate, and identify these serum DNA sequences, enabling very early detection of an underlying disease state or of a change in response to treatment. In the current study, the researchers were able to identify specific signature sequences in serum DNA before clinical symptoms appeared in animals experimentally infected with BSE (bovine spongiform encephalopathy or mad cow disease). "These new results add to the growing body of scientific data validating the value of serum DNA as an early indicator of disease, and also advance our unique ability to apply these findings to the development of laboratory tests for routine clinical use," said Dr. Howard Urnovitz, CEO of Chronix, and one of the authors of the study. "Using our proprietary technology and next-generation sequencers, we were able to identify distinctive DNA signatures indicating the presence of BSE in all of the infected animals well before clinical symptoms appeared." These new findings follow three previous published studies demonstrating the utility of using serum DNA to identify human cancers, human infectious disease, and BSE. [Press release] [Zoonoses and Public Health abstract]