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Liver-Targeted Drug Stops Hepatitis C

Durable DNA Molecule Blocks Hepatitis C Virus in Chimp Study
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WebMD Health News
Reviewed by Louise Chang, MD

Dec. 3, 2009 -- Hepatitis C virus can't get a grip on the livers of chimps treated with a new antisense DNA drug.

The drug, dubbed SPC3649, doesn't attack the hepatitis C virus (HCV) itself. Instead, it blocks the tiny RNA molecules in the liver -- microRNA-122 or miR-122 -- that the virus must use to make new copies of itself. HVC causes disease only when it can replicate to high liver concentrations.

HCV levels drop 350-fold in chimps treated with SPC3649, find Robert E. Lanford, PhD, of San Antonio's Southwest foundation for Biomedical Research and colleagues.

"The drug worked exceptionally well in treating HCV infections in chimpanzees," Lanford said in a news release. In an email to WebMD he said, "We were very excited with the outcome."

The researchers studied four chimps chronically infected with HCV genotype 1, the most common HCV strain in the Americas and Australia. It's also the most treatment-resistant HCV strain.

Two chimps got a low dose of SPC3649, and two got a high dose, given once a week for 12 weeks. The higher-dose treatment was remarkably effective in suppressing HCV. The lower dose showed a strong but lesser effect in one chimp, but not in the other.

As long as the animals stayed on the drug -- and for two weeks after treatment stopped -- HCV levels remained low. But after treatment ended, HCV levels eventually rebounded to pretreatment levels.

Treatment, however, made the virus much more sensitive to the antiviral effects of interferon. Interferon, combined with ribavirin, is the best current treatment for HCV, but only about half of people infected with genotype 1 HCV get long lasting control of the virus. It's hoped that SPC3649 could eventually be combined with interferon to give the virus a knockout punch.

SPC3649 targets miR-122 in the liver, where it plays a role in cholesterol metabolism. The only side effect seen in the chimps was a rather dramatic lowering of LDL (bad) cholesterol. In earlier studies with green monkeys, the drug had a stronger effect on HDL (good) cholesterol. That would not be a good thing if it happens in humans, but SPC3649 affects cholesterol differently in different primate species.

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