Discovery of new anthelminthic drugs
Worm infections - a challenge
Parasitic worms (helminths) are causing serious health problems and economic damage worldwide. Mass treatment of humans and animals has led to rising numbers of resistances to anthelminthic drugs. Only few agents are available for treating worm infections, thus, new anthelminthic drugs are required.
Several flies with one flap
Due to similarities among parasitic worms, new anthelminthics will quite likely protect against a variety of helminth species just as praziquantel, the present drug of choice against schistosomiasis, is active against many trematodes and tape worms. This is of interest also for the large market of livestock.
So far, we have identified several candidates from screening libraries of approved drugs and 400 agents contained in the Malaria Box. Screening is performed in collaboration with Fraunhofer IME ScreeningPort, a research institution with a wide ranging experience in pharmaceutical industry R&D and access to large compound libraries, and with Merck, a key player in the global fight against schistosomiasis.
To screen approved drugs — i.e. drugs validated for therapeutic use — is attractive, because toxicity studies have already been performed on these compounds and many of their side effects are known. Thus, much of the early cost and time needed to bring a drug to the market may be saved by this approach, so-called drug repurposing.
While most FDA-approved drugs do not affect schistosome development in vitro, some clearly do!
Praziquantel, the present drug of choice against schistosomiasis, profoundly damages the worms.
The white cell clusters reflect an activated immune defence necessary to complete praziquantel-induced killing.
Freshly transformed schistosome larvae were cultured for two weeks in the presence or absence of approved drugs (10 µM).
In the absence of drugs ("negative control") larvae develop normally with dark-brown horseshoe-shaped guts typical for two-week old schistosomes.