Hepatitis C drug goes after patients’ RNA

No matter what medications doctors throw at hepatitis C, it continues to defy treatment in some patients. But a new compound offers an approach quite apart from the rest: It assaults a kind of RNA that is implicated in allowing the virus to gain a foothold.

In most of a small group of patients who took the experimental drug, virus levels were knocked down, sometimes below the threshold of detection. The drug does this by targeting genetic material in the liver called microRNA-122. The hepatitis virus normally attaches to this RNA, gaining the stability it needs to propagate while hiding from immune system patrols.

The new drug, called miravirsen, binds to microRNA-122, sequesters it and indirectly thwarts viral replication, says study coauthor Harry Janssen, a hepatologist and physician at the University of Toronto. Janssen and colleagues report the findings March 27 in the New England Journal of Medicine.

The technique could have broad applicability, because microRNAs — genetic material that regulates some gene activity — can play roles in cancer and other ailments (SN: 8/28/2010, p. 18). The strategy is “a whole new approach to the treatment of serious disease,” says Phillip Sharp, a molecular biologist at MIT who earned a 1993 Nobel Prize for work on RNA. “This is an additional treatment that looks quite interesting and almost certainly will be used at some level,” he says.

For the study, researchers randomly assigned 36 people with hepatitis C to get five weekly injections spaced over a month. Nine were given placebo shots while 27 got varying doses of miravirsen. No study participant had received any hepatitis drugs beforehand. The scientists monitored the patients for 18 weeks.

While those given the placebo showed little or no improvement, most who received the drug experienced a drop in virus levels. The 18 patients at the two highest dose levels showed profound reductions in viral RNA during the study period. Five of those 18 patients had undetectable virus levels at some point after treatment.

A few patients in each subgroup also received interferon — a standard treatment for hepatitis C — during the trial. At the end of the study, four patients getting both drugs and one getting miravirsen alone still showed no detectable virus — 14 weeks after the last shot.

Some experts worry that because microRNA-122 affects certain liver functions — including cholesterol synthesis — a drug inhibiting the microRNA might cause serious side effects. But patients in this trial showed only mild effects.

In the body, miravirsen has a half-life of roughly 30 days, Janssen says, suggesting that it might work as a monthly injection. Pairing it with another medicine might work even better, he adds. The new drug may dodge viral resistance to current drugs because it targets the host, not the virus.

MicroRNAs were discovered only 20 years ago, and research in the field is moving rapidly, Sharp says. “This is really a revolution in science,” he says, “and it’s now beginning to be translated into advances that control disease.”