This five-year $164,160 K23 project grant award from the National Institute of Child Health and Human Development (CFDA 93.865 - Child Health and Human Development Extramural Research) supports Dr. Gelineau-Morel's research to develop a precision dosing model for the use of trihexyphenidyl in children with dystonia and cerebral palsy.
The key objectives of this project are to: 1) Determine the impact of CYP2D6 and CYP2C19 genotypes on exposure to the two enantiomers of trihexyphenidyl, 2) Develop a pediatric physiologically-based pharmacokinetic (PBPK) model to simulate exposures based on individual pharmacogenetics, age, weight, and sex, and 3) Establish the feasibility of a future exposure-controlled clinical trial of trihexyphenidyl for dystonia associated with cerebral palsy. This research aims to enable more personalized dosing to maximize therapeutic benefit and minimize side effects for this patient population.