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New drug technology produces marked improvement in hepatitis C therapy in animals

Date:
December 3, 2009
Source:
Southwest Foundation for Biomedical Research
Summary:
In a dramatic finding, a new drug for hepatitis C virus (HCV) infections that targets liver cells produced a substantial drop in blood levels of the virus in animals and continued to work up to several months after treatment.

In a dramatic finding, a new drug for hepatitis C virus (HCV) infections that targets liver cells produced a substantial drop in blood levels of the virus in animals and continued to work up to several months after treatment, say scientists at the Southwest Foundation for Biomedical Research (SFBR) in San Antonio.

The drug, SPC3649, was developed by the biopharmaceutical firm Santaris Pharma A/S in Denmark using their proprietary nucleic acid chemistry called "locked nucleic acid" or LNA. SPC3649 is a nucleic acid, or DNA-based drug, that captures a small RNA molecule in the liver, called microRNA122, that is required for HCV replication.

"Our collaboration with Santaris Pharma proved that the drug worked exceptionally well in treating HCV infections in chimpanzees," said SFBR's Robert Lanford, Ph.D., the lead author on the study appearing in the December 3, 2009 issue of Science Express, which provides rapid electronic publication of research papers ahead of print in the journal Science.

SPC3649 also showed a high barrier to resistance, a major problem with therapies that directly target the virus. Moreover, this proof of concept study suggests that the technology might also prove useful in treating many other diseases such as HIV, cancer, and inflammatory diseases.

HCV infections affect 170 million people worldwide and progress over years to end stage liver disease including cirrhosis and liver cancer. In the United States, 4 percent of the adult population is chronically infected with HCV. The only U.S. Food and Drug Administration approved therapy is interferon and ribavirin, which is very toxic, requires 48 weeks of treatment and works in less than half of patients. Scientists believe that a cocktail of three drugs will be needed to prevent antiviral resistance and replace interferon.

The new therapy could potentially replace interferon in future cocktails, since it provides a high barrier to resistance. "This antiviral could be used alone to treat disease progression and there are indications that it can convert interferon non-responders to responders, so that non-responders to the current therapy could be treated with the combination of this drug with interferon," Lanford said. It may also be a good therapy to use after transplant, since it may help suppress HCV in the new liver. It has no toxic or adverse reactions and this is critical in the transplant setting.

In the study, four HCV chronically infected chimpanzees were treated with the new antiviral. The two animals that received the higher dose had a drop in viral levels in the blood and liver of 2.5 orders of magnitude or approximately 350 fold. The surprising findings were the lack of antiviral resistant mutants and the fact that the therapy continued to work for several months after dosing stopped.

In one advance, the new study was a critical proof of concept that the LNA technology could work for HCV. It proved that miR-122 was truly required for HCV replication in an animal infected with HCV. Previously the role of miR-122 in HCV replication had only been shown in tissue culture. A second advance was the finding that LNA therapy could work against an important disease model, suggesting that the new technology can be applied to other diseases.


Story Source:

The above story is based on materials provided by Southwest Foundation for Biomedical Research. Note: Materials may be edited for content and length.


Cite This Page:

Southwest Foundation for Biomedical Research. "New drug technology produces marked improvement in hepatitis C therapy in animals." ScienceDaily. ScienceDaily, 3 December 2009. <www.sciencedaily.com/releases/2009/12/091203141852.htm>.
Southwest Foundation for Biomedical Research. (2009, December 3). New drug technology produces marked improvement in hepatitis C therapy in animals. ScienceDaily. Retrieved September 18, 2014 from www.sciencedaily.com/releases/2009/12/091203141852.htm
Southwest Foundation for Biomedical Research. "New drug technology produces marked improvement in hepatitis C therapy in animals." ScienceDaily. www.sciencedaily.com/releases/2009/12/091203141852.htm (accessed September 18, 2014).

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