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

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.

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.

"I suspect that at some point lowering HDL too much would be a problem if you did not lower LDL at the same time," Lanford said in his email. "I do not suspect that this will be a limitation of this drug, but human clinical trial data are needed to address this issue."

That data is on the way. The drug's manufacturer, Santaris Pharma of Hoersholm, Denmark, has begun a phase 1 safety trial in HCV patients. Santaris funded the Lanford study and Santaris researchers contributed to the work.

The Lanford study was published online in the Dec. 3 issue of Science Express.