A new drug can take about 14 years and $1 billion to develop. As one way to help speed the development of new disease therapies, rather than starting from scratch, NCATS researchers test existing medicines for their potential to treat other diseases.
Recently, NCATS scientists, in collaboration with researchers from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), discovered that an over-the-counter drug used to treat allergy symptoms also limited hepatitis C virus (HCV) infection in human liver cells. The findings suggest that the drug, chlorcyclizine HCl (CCZ), potentially could be used to treat this chronic infection in people. Results were published April 8, 2015, in Science Translational Medicine.
An estimated 185 million people worldwide suffer from HCV infection. It causes liver inflammation and often leads to serious complications such as cirrhosis, which can be fatal. Early diagnosis and treatment of HCV infection can prevent liver damage.
The NCATS researchers (see sidebar) collaborated with NIDDK’s Jake Liang, M.D., in using the Center’s high-throughput screening capabilities to look for compounds that blocked viral activity in HCV-infected human liver cells. The team tested the NCATS Pharmaceutical Collection, a library containing approved and investigational drugs, and identified CCZ, an antihistamine, as a promising candidate that appeared to limit the early stages of HCV infection. The effect was enhanced when the researchers combined CCZ with existing HCV drugs, suggesting CCZ could be an effective add-on to current treatments.
Next, the team gave CCZ to HCV-infected mice and found that the compound significantly reduced viral infection. The treated mice showed no signs of drug resistance, a common problem among existing HCV therapies. The study results suggest CCZ, with its well-established safety profile as an allergy drug, could be a more broadly accessible treatment for HCV infection.
Scientists still have much to learn from approved drugs and their untapped potential to help researchers understand basic biology and develop treatments for unmet medical needs. In addition to HCV, other NCATS repurposing screens have identified potential drug candidates for a variety of illnesses, from blocking Ebola virus infection to reversing multiple sclerosis.
The study in mice provided data that validated chlorcyclizine’s activity. Based on the results, the team worked through the Food and Drug Administration to quickly move this discovery from the lab to testing of CCZ in patients with HCV infection at the NIH Clinical Center.
Posted April 2015