MINOCYCLINE IN PSC

Primary sclerosing cholangitis (PSC) is characterized by chronic inflammation of the bile ducts, which may lead to liver failure and/or malignant transformation and development of cholangiocarcinoma. Today, there is no specific therapy available to prevent or even delay the development of these fatal complications. Here we propose a novel therapeutic approach where we target the production and the release of nitric oxide (NO).

NO is produced by inducible nitric oxide synthase (iNOS), which is known to be upregulated in PSC, potentially contributing to the chronic inflammation and malignant transformation. We have chosen a drug, minocycline, which by inhibiting iNOS activity, potentially reduces the inflammation of the bile ducts. The aim of this open-label pilot study is to evaluate the safety and estimate the efficacy at the maximally tolerated dose, 100mg bid, in 30 patients with PSC. Liver biochemistries and Mayo risk score after 12 months of treatment will be determined and compared to baseline values. A positive study will establish the basis for further evaluation of minocycline in a large number of patients in the context of a placebo-controlled trial.