Protein kinases, potential targets of novel treatment strategies
Protein kinases, potential targets of novel treatment strategies
For decades, Praziquantel (PZQ) is the drug of choice for schistosomiasis treatment and a vaccine is not available. With respect to first evidence of the possibility of upcoming PZQ resistance1,2, great efforts are undertaken worldwide to find new chemotherapeutic options for treatment.
Protein kinases (PKs) are essential members of signal transduction cascades that mediate molecular communication processes within and between cells. In this respect PKs are indispensable to life. Because aberrant PK functions take distinctive roles in human diseases they represent targets in chemotherapies. Results of research activities from our lab have shown that conserved PKs exist in Schistosoma mansoni and perform a broad spectrum of activities contributing among others to reproduction processes and the maintenance of tissue integrity3,4. Exploiting the similarity of PKs of humans and schistosomes (as well as other parasites), PK inhibitors designed for the treatment of human diseases (such as Imatinib, a cancer drug; see image) may serve as lead compounds for new drugs against schistosomiasis (and further infectious diseases caused by parasites). First research results in this research area have confirmed that this approach is promising for fighting schistosomes4-8 but also other parasites8-12. A case report of a 29-years old women infected with fliariae showed a therapeutic effect of Imatinib15.
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Schistosome couples before (left) und following treatment with Imatinib (right) in vitro. Without treatment adult schistosomes suck with their ventral suckers to the Petri dish, and they perform wave-like movements. Pairing is stable, and the female resides within the ventral grove of their male partner (see movie 1). Following Imatinib treatment the couples separate. The worms do not suck anymore, they lie on the side, get stiff, and die finally (see movie 2). Bulge-like swelling are frequently observed in the gonads (see star) and the gastrodermis4. |
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Movie 1: Untreated schistosome couple4
Movie 2: Schistosome couple treated with Imatinib4
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