New Drug Targets Liver MicroRNA and Blocks Hepatitis C Virus Replication

A promising new treatment for hepatitis C is based on a drug that blocks the action of a microRNA (mRNA) produced by liver cells that are required by the virus in order to replicate.

Hepatitis C is a major health problem with an estimated 3% of the world's population infected with the virus and an additional 170 million people who are chronic carriers at risk of developing liver cirrhosis and/or liver cancer. The current treatment for hepatitis C, which combines pegylated interferon-alpha with ribavirin, is effective in only about 50% of patients and is often associated with severe side effects. Furthermore, the virus frequently mutates, which renders the treatment ineffective.


A possible breakthrough in the treatment of hepatitis C has been reported by investigators at Santaris Pharma A/S (Hørsholm, Denmark) and their collaborators at the Southwest Foundation for Biomedical Research (San Antonio, TX, USA). They wrote in the December 3, 2009, online edition of the journal Science that the drug SPC3649, which had been developed using Santaris' proprietary Locked Nucleic Acid (LNA) Drug Platform, successfully blocked the liver microRNA, miR-122. Inhibition of miR-122 activity prevented the hepatitis C virus from replicating and significantly reduced the numbers of hepatitis C viruses in the bloodstream of chronically infected chimpanzees.

SPC3649 is one of the first microRNA-targeted drugs to enter human clinical trials and is currently undergoing Phase 1 clinical studies in healthy volunteers. The Locked Nucleic Acid (LNA) Drug Platform used to develop SPC3649 creates synthetically modified chemical versions of the normal nucleic acid building blocks of ribonucleic acids (RNA). These modified chemical versions called LNAs improve the drug-like qualities of resulting therapeutic agents by improving affinity to their target RNA, boosting resistance to metabolism, and improving tissue uptake.

"Advancing the first microRNA-targeted therapy, SPC3649, into human clinical trials was certainly a breakthrough in science and we are very encouraged by these preclinical findings demonstrating that SPC3649 has the potential to be an effective treatment for patients infected with the hepatitis C virus," said Dr. Henrik Ørum, chief scientific officer of Santaris Pharma A/S. "In drug discovery and development programs internally and with our partners, we continue to demonstrate that our proprietary LNA Drug Platform is fundamental in developing effective RNA-targeted therapies with high affinity, target specificity and remarkable potency for a range of diseases."

Related Links:
Santaris Pharma A/S
Southwest Foundation for Biomedical Research