For several years, the biomedical research community has recognized that compounds already approved for human use might have additional therapeutic applications. To facilitate investigation of new applications for existing drugs, the US National Institutes of Health (NIH) assembled several collections of molecules that can be screened for specific characteristics. Two recent papers report the screening of these collections together with animal testing to identify promising new uses for approved drugs.

T. Jake Liang (NIH, Bethesda, MD) and colleagues screened the NIH Chemical Genomics Center Pharmaceutical Collection to detect compounds with activity against hepatitis C virus (HCV). HCV infection can become chronic, leading to liver disease, cirrhosis and cancer. Currently available treatments are costly and have unwanted side effects. “Although hepatitis C is curable, there is an unmet need for effective and affordable medication,” Liang told NIH Research Matters. His research group discovered antiviral activity in chlorcyclizine HCl (CCZ), an over-the-counter antihistamine drug approved for the treatment of allergy symptoms. CCZ inhibited HCV infection in human liver cells in vitro. CCZ also limited HCV infection in mice with engrafted human liver cells for 4–6 weeks without eliciting drug resistance. “CCZ represents a promising candidate for drug repurposing and further development as an effective and accessible agent for treatment of HCV infection,” the group concluded (Sci. Transl. Med. 7, 282ra49; 2015).

Robert H. Miller (George Washington University, Washington, DC), Paul J. Tesar (Case Western Reserve University, Cleveland, OH) and collaborators searched a separate library called the NIH Clinical Collections for drugs able to trigger maturation of oligodendrocyte progenitor cells (OPCs) into oligodendrocytes, which are responsible for myelination of nerve cells. This maturation process is faulty in multiple sclerosis (MS), resulting in reduced myelination and chronic disability. The researchers identified two compounds, miconazole (an antifungal) and clobetasol (a steroid), that stimulated OPC maturation and remyelination. Both drugs improved remyelination in a mouse model of focal demyelination and promoted precocious myelination in the absence of disease in young mouse pups. The drugs also induced differentiation of human OPCs into oligodendrocytes. Clobetasol but not miconazole reduced disease severity in an immune-mediated mouse model of MS, and both compounds were effective in a chronic mouse model of MS, with nearly all the treated animals regaining use of at least one hind limb (Nature 10.1038/nature14335; published online 20 April 2015). The scientists believe that “these drugs... could advance into clinical trials for the currently untreatable chronic progressive phase of MS.”