Cancer deaths in Korea

Institut Pasteur Korea and Sanofi look for small-molecule antiviral to combat HBV

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SEOUL, South Korea—One of the most common and seriousinfectious diseases, hepatitis B—which accounts for a staggering 38 percent ofall cancer deaths in Korea—is to be targeted in a new collaborative venturebetween the translational research institute, Institut Pasteur Korea (IP-K),and Sanofi-Aventis Korea. The goal is to develop and validate a high-throughputassay to screen IP-K's chemical libraries for novel compounds that can bedeveloped as new drugs.
Under the terms of the agreement, Sanofi will fund theinitial phase of the project that is anticipated to last for a year, afterwhich IP-K and Sanofi will jointly determine which compounds should be broughtforward for optimization and further development. The collaboration was madepossible by the Global Alliance Project framework, which Sanofi-Aventis Korealaunched with Korean trade and health industry development groups, KOTRA andKHIDI, in June 2009.
Despite the availability of medicines and a vaccine, IP-Kestimates that about 5 percent of the global population, or about 350 millionpeople worldwide, are chronic carriers of the hepatitis B virus (HBV). As muchas 8 percent of the population in some Asian countries, including Korea andChina, are at risk of progressing onto liver cirrhosis and cancer. In a 10-yearprospective cohort study of liver cancer in Korea involving 3,807 individualswho died from liver cancer during the period, researchers found that thepopulation that was positive for hepatitis B surface antigen (HBsAg) was 24.3times (males) and 54.4 times (females) more likely to progress to cancer thanindividuals whose status was negative. The study also evaluated cigarettesmoking and heavy alcohol consumption and found these factors to be associatedwith increased risk of mortality from hepatocellular carcinoma but at a muchlower relative risk of from 1.1 to 1.5. The risk factors did not interactsynergistically, the authors reported in the Journal of the National CancerInstitute in 2004.
Perhaps coincidentally, the independent nonprofit instituteIP-K was founded in April 2004 with a strategic focus on enabling technologiesand therapeutic development in disease models pertaining to public health. IP-Khas developed "a novel research platform that combines chemical genomics withhigh-content visual screening by bringing together the latest advances inbiology, technology and chemistry. The application of the platform technologyin the fields of infectious disease and chronic illness allows basic science tobe extended to drug discovery. In turn, the application of functionalgenomics—using global siRNA—allows further elucidation of the basic molecularand genetic underpinnings of disease," states the institute's media releaseannouncing the Sanofi alliance.
The joint research effort sprang from the laboratory of Dr.Wang-Shik Ryu of the Department of Biochemistry at Yonsei University in Seoul.The study cited above came out of the graduate school of public health atYonsei U.
"This new research collaboration provides a textbook exampleof modern drug discovery in action," says Dr. Marc Windisch, who will lead theteam at IP-K. "It brings promising basic research from an academic laboratoryinto the high-throughput translational research environment at IP-K."
IP-K researchers are developing cellular models to identifyinhibitors that target a specific step in the viral life cycle—the assembly ofthe HBV capsid. This approach is aimed at preventing the release of infectiousvirus particles into the bloodstream, thereby reducing the viral load inpatients. Once perfected, the IP-K cellular models will be used tocomprehensively screen the institute's compound libraries for novel antiviralinterventions. Currently, most available HBV drugs inhibit reversetranscription, the process by which the virus RNA is transcribed into DNA forreplication. However, new therapies are needed to compensate for the emergingresistance of the virus to these drugs.
Once promising small molecules have been identified, Sanofiwill take the leads through optimization, development and commercialization. 
"Our open-innovation strategy is to elucidate Asian-specificdiseases and to collaborate with leading institutions," said Frank Jiang, vicepresident and head of TSU Asia Pacific R&D at Sanofi. "The translationalcapabilities of IP-K will facilitate the discovery of drugs based on novelmechanisms to combat HBV."

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