The Multiple Drug Resistance Gene, Polymorphisms, and uses Thereof
Introduction Multiple drug resistance is a well-documented phenomenon and critical problem in the treatment of various diseases including cancer and HIV. While there are many mechanisms leading to multiple drug resistance, one area of focus is the MDR1 gene and its protein product P-glycoprotein (Pgp). Pgp functions as a membrane channel that removes drugs from cells. By increasing Pgp activity, removal of drugs from diseased cells is accelerated, making the drugs ineffective. Pgp is able to export a wide variety of drugs including numerous chemotherapy drugs and HIV protease inhibitors. Circumventing multiple drug resistance caused by changes in Pgp function will require knowledge of mutations (polymorphisms) that affect function and designing drugs that are not affected by these mutations. Technology description Dr. Rodney Ho at the University of Washington has identified novel Pgp mutations that he has shown affect the ability of Pgp to export drugs from cells in vitro. In addition, Dr. Ho has created cell lines that express these genes and that have been optimized to study drug exportation by the Pgp isoforms as well as to screen for drugs that are not affected by these mutations. Business opportunity Potential markets include biotechnology and pharmaceutical companies that are identifying and developing drugs to treat numerous diseases including cancer and HIV. There is also opportunity in personalized medicine/pharmacogenomics as the functional mutations may be used to determine effectiveness of a given drug for a particular patient. Stage of development There has been significant validation of the functional effects of the Pgp polymorphisms. Discovery and validation of additional polymorphisms is on-going. Intellectual property position The UW has a US application pending that includes extensive supporting data.
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