Bladder pain and injury - whether caused by chemotherapy effects, surgery, indwelling catheters, or pain syndromes - collectively affect millions of patients. Few drugs directly treat bladder pain, and the current standard of care to prevent chemotherapy-induced hemorrhagic cystitis (which encompasses bladder pain, blood in the urine, and irritative bladder symptoms) is unreliable at best, and can cause adverse drug reactions at worst. New research published online in The FASEB Journal reveals the therapeutic potential of H-IPSE - a host immunomodulatory protein produced by the eggs of the urogenital parasitic worm Schistosoma haematobium - in a mouse model of chemotherapy-induced hemorrhagic cystitis.
A research team led by Michael Hsieh, MD, PhD, Associate Professor of Urology and Pediatrics at George Washington University and Stirewalt Scientific Director at Biomedical Research Institute, used multiple control and experimental groups to conduct the experiment. Controls included mice given ifosfamide (the agent that causes hemorrhagic cystitis) without H-IPSE; mice given ifosfamide and H-IPSE; mice given ifosfamide and IL-4 (which also can alleviate hemorrhagic cystitis); mice given ifosfamide and Mesna (the current standard of care for chemotherapy-induced hemorrhagic cystitis); mice given ifosfamide and H-IPSE with anti-IL-4 antibody; and mice given ifosfamide with a mutant version of H-IPSE.
The animal study confirmed that H-IPSE exerts a potent therapeutic effect on chemotherapy-induced hemorrhagic cystitis. The researchers also found that a portion of H-IPSE's effect seems to depend on a nuclear localization sequence, suggesting that H-IPSE changes host cell transcription.
"Our findings suggest that urogenital parasite proteins that alter host biology can be therapeutically exploited to treat bladder pain," said Hsieh. "This work also demonstrates the untapped potential of parasitic proteins as novel therapeutics. Parasites have co-evolved with their human hosts for millennia and thus have very evolved genes. We can turn this biology on its head for therapeutic exploitation."
"Given the pain and suffering it inflicts worldwide, turning something in this creature to a therapeutic purpose is exciting, has a touch of irony, and a moment of hope," said Thoru Pederson, PhD, Editor-in-Chief of The FASEB Journal.
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FASEB is composed of 30 societies with more than 125,000 members, making it the largest coalition of biomedical research associations in the United States. Our mission is to advance health and well-being by promoting research and education in biological and biomedical sciences through collaborative advocacy and service to our societies and their members.