Therapeutic exploitation of IPSE, a urogenital parasite-derived host modulatory protein, for chemotherapy-induced hemorrhagic cystitis

  • Evaristus C. Mbanefo, Loc Le, Luke F. Pennington, Justin I. Odegaard, Theodore S. Jardetzky, Abdulaziz Alouffi, Franco H. Falcone, Michael H. Hsieh
  • The FASEB Journal, August 2018, Federation of American Societies For Experimental Biology (FASEB)
  • DOI: 10.1096/fj.201701415r

What is it about?

Ifosfamide and cyclophosphamide are chemotherapy drugs used to treat many cancers. These drugs can cause a devastating complication of the bladder, hemorrhagic cystitis, which features extensive bladder damage, including severe bleeding and pain. The main drug used to prevent hemorrhagic cystitis, Mesna, can also cause its own complications, and sometimes does not successfully prevent hemorrhagic cystitis. Thus, there is a need for alternatives to Mesna._x000D_ _x000D_ The urogenital parasitic worm, Schistosoma haematobium, lays thousands of eggs in the host human bladder each day, and yet most infected people do not exhibit the degree of bladder pain and bleeding that one would expect from heavy infection. We hypothesized that this may be due to parasite production of factors which alleviate the hemorrhagic cystitis caused by infection, and that these factors could be used to alleviate ifosfamide-induced hemorrhagic cystitis._x000D_ _x000D_ One of these parasite factors, the Schistosoma haematobium version of Interleukin-4-inducing principle from Schistosoma mansoni Eggs (H-IPSE), is very therapeutic in a mouse model of ifosfamide-induced hemorrhagic cystitis, and in fact one dose of H-IPSE is superior to multiple doses of Mesna._x000D_ _x000D_ This work represents the first time that a urinary pathogen molecule has been therapeutically "exploited" in a clinically relevant bladder disease model, and indicates that H-IPSE may be an alternative to Mesna for reducing ifosfamide-induced hemorrhagic cystitis.

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The following have contributed to this page: Michael Hsieh, Franco Falcone, and Abdulaziz Alouffi