Helminth ABC Transporters as Targets for Combination Therapy

Robert Greenberg of the University of Pennsylvania in the U.S., along with Bernadette Ardelli of Brandon University in Canada, will test whether anthelmintics, which are drugs used to treat diseases caused by parasitic worms, can be improved by combining them with inhibitors of ATP-binding cassette (ABC) multidrug transporters. Of the few anthelmintics available, many are of limited use or become ineffective due to the emergence of drug resistance. ABC multidrug transporters regulate the transport of molecules, including drugs, into and out of the cell and have been linked with anthelmintic resistance. ABC transporter inhibitors, which have been approved for use in humans, enhance the activity of anti-parasitic drugs in vitro and may bypass the development of drug resistance. The investigators will use in vivo mouse models of helminth infections to test whether co-administering ABC transporter inhibitors enhances anthelmintic activity, with a view to carrying out clinical trials in humans.