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Drug Thwarts Hepatitis C
27 October 2003 (All day)
The first drug designed to target hepatitis C beat back the liver-ravaging virus in a small clinical trial. The results offer hope that drugs that disable the virus's enzymes could ultimately help rid the body of hepatitis C and save thousands of people from cirrhosis and liver cancer.
Hepatitis C virus (HCV) infects 170 million people worldwide. About 70% develop liver disease, and in America alone, more than 10,000 die from it each year. Today's best treatment, a combination of the drugs interferon and ribavirin, eliminates virus from less than half of all patients treated. It also hits the body hard, causing anemia, fever, fat-tissue damage, and depression. To lessen side effects, at least half a dozen drug companies have pursued compounds that home in on the virus while leaving human cells alone. Daniel Lamarre and his colleagues at Boehringer Ingelheim in Laval, Quebec, focused on blocking an enzyme called NS3 that helps HCV produce the proteins it needs to survive and multiply.
The researchers started with a floppy peptide molecule that slowed but did not stop NS3. Then they tinkered with the peptide by adding chemical groups that made it stiffer and better able to fit into the enzyme's active site. The drug, called BILN 2061, blocked a crippled version of HCV from reproducing in cultured liver cells, and no serious side effects appeared in animals and healthy human volunteers, the company says. To see if it stopped the virus, the researchers had eight patients drink either a placebo or a solution containing BILN 2061 twice a day for 2 days. According to results published online 26 October in Nature, the virus level typically plummeted more than 100-fold in patients that drank BILN 2061. It takes 12 weeks for interferon and ribavirin to reduce virus levels the same amount.
"This is a very important proof of principle for using specific viral inhibitors to treat hepatitis C," says hepatologist Adrian Di Bisceglie of Saint Louis University in Missouri. But the virus could still adapt quickly to BILN 2061 and become resistant, he cautions. And the company has not yet proven that the drug is safe for long-term treatment. "It's a big unanswered question."