Session 1E: Examining Cytochrome P450 Reductase as a Drug Target against Human Schistosomiasis
Session Number
Session 1E: 3rd Presentation
Advisor(s)
David Williams, Rush University Medical Center
Location
Room A113
Start Date
28-4-2017 8:30 AM
End Date
28-4-2017 9:45 AM
Abstract
Schistosomiasis is a debilitating waterborne disease which affects 260 million people annually in poverty-stricken regions in Africa, Southeast Asia, and South America. Three species of worm transmit schistosomiasis in its larval stage through unsanitary water conditions. Only one drug, praziquantel, exists to combat schistosomiasis, but due to the disease’s prevalence, drug resistance is expected to develop soon. One protein that has been found to be essential to these worms’ pathology is cytochrome p450 which, in humans, functions as a detoxifying agent. While its function in worms is currently unknown, studies have shown that p450 is essential to the worm’s survival. Therefore, inhibiting its reducing agent, cytochrome p450 reductase (CPR), may effectively kill the worm. To test CPR’s potential as a drug target, our investigation aimed to characterize and understand its function in Schistosoma mansoni, the species which accounts for 40% of schistosomiasis worldwide. Through amplification, cloning, and sequencing, we have found that CPR in S. mansoni lacks a sequence found in the human and other schistosomes’ CPR. This difference between S. mansoni and humans may prove very important for CPR’s potential drug development, as the added sequence in the human CPR can prevent the host proteins from being targeted when the drug acts on S. mansoni CPR.
Session 1E: Examining Cytochrome P450 Reductase as a Drug Target against Human Schistosomiasis
Room A113
Schistosomiasis is a debilitating waterborne disease which affects 260 million people annually in poverty-stricken regions in Africa, Southeast Asia, and South America. Three species of worm transmit schistosomiasis in its larval stage through unsanitary water conditions. Only one drug, praziquantel, exists to combat schistosomiasis, but due to the disease’s prevalence, drug resistance is expected to develop soon. One protein that has been found to be essential to these worms’ pathology is cytochrome p450 which, in humans, functions as a detoxifying agent. While its function in worms is currently unknown, studies have shown that p450 is essential to the worm’s survival. Therefore, inhibiting its reducing agent, cytochrome p450 reductase (CPR), may effectively kill the worm. To test CPR’s potential as a drug target, our investigation aimed to characterize and understand its function in Schistosoma mansoni, the species which accounts for 40% of schistosomiasis worldwide. Through amplification, cloning, and sequencing, we have found that CPR in S. mansoni lacks a sequence found in the human and other schistosomes’ CPR. This difference between S. mansoni and humans may prove very important for CPR’s potential drug development, as the added sequence in the human CPR can prevent the host proteins from being targeted when the drug acts on S. mansoni CPR.