WASHINGTON - Children's National Health System Urologist Michael Hsieh, M.D., was awarded a National Institutes of Health (NIH) grant to optimize a set of parasite proteins that could alleviate pain in multiple types of bladder inflammation.
The $1 million R01 grant will fund a five-year study to exploit a parasite-derived protein, IPSE, as a candidate therapeutic. Dr. Hsieh hypothesizes that IPSE may have the ability to modulate host immune and non-immune responses to bladder injury. IPSE could be optimized for therapeutic potential, while minimizing toxicity, by generating forms that have the ability to modulate host responses via three distinct mechanisms: IL-4-binding, chemokine-binding and nuclear localization.
"Painful bladder syndromes affect up to 40 percent of patients and effective therapies do not exist for many of these patients," says Dr. Hsieh. "In the past, our research focused on understanding pathogens and their interaction with other agents. Now, we are turning the biology on its head and using them to eliminate pain."
Using what is already known about the sequence and structure of IPSE, Dr. Hsieh and his research team will use targeted and random methods to generate mutant forms of IPSE, and test their ability to alleviate bladder pain. The team will also screen these mutants for low toxicity in various tests. The long-term goal is to develop IPSE as a possible alternative to opioids for treating pain in general, which would greatly expand its therapeutic potential.
Dr. Hsieh joins a very small group of seven pediatric urologists in the country who received the R01, the oldest grant mechanism used by NIH. Dr. Hsieh and his team will collaborate with Theodore Jardetzky, professor of structural biology at Stanford University, and Franco Falcone, associate professor in allergy and infectious diseases, Faculty of Science at University of Nottingham in the U.K.