ASTS gratefully acknowledges Veloxis Pharmaceuticals for their sponsorship of the 2017 Vanguard Prizes.
Post-transplant immunosuppressive drugs such as tacrolimus have narrow and inconsistent therapeutic target ranges. Inter- and intra-individual variability in dosing requirements necessitates empirical physician-titrated drug administration that results in frequent deviation from target ranges and can result in rejection, infection, or other toxicities. Multiple studies point to the importance of aggressive dosing and monitoring to minimize the risk of acute rejection and drug toxicities. The large array of genetic, environmental, and physiological factors that affect drug dose response make generating a predictive model-based algorithm for drug dosing very difficult. Conventional approaches to transplant immunosuppression present important challenges to regulating drug levels in the blood as several drugs are often co-administered, making it very difficult to accurately determine how patients will respond to variations in their therapy. A robust procedure to achieve individualized responses to the co-administration of multiple post-transplant drugs has thus far not been able to respond adequately to inter- and intra-patient variability that results from genetic/pharmacokinetic and other individualized factors. We have developed a computational approach named Phenotypic Precision Medicine (PPM) to utilize empirical clinical data to construct patient-specific visual maps that represent each individual’s phenotypic response to drug treatment. These visual maps then would allow us to rapidly pinpoint dosing parameters for that individual. Importantly, because this process does not require any a priori knowledge of disease mechanism, it can efficiently personalize drug dosing despite frequent changes to treatment regimens following transplantation.