Inhibition of pyruvate dehydrogenase kinase improves pulmonary arterial hypertension in genetically susceptible patients

Authors: Evangelos D. Michelakis, Vikram Gurtu, Linda Webster, Gareth Barnes, Geoffrey Watson, Luke Howard, John Cupitt, D. Ian Paterson, Richard B. Thompson, Kelvin Chow, Declan P. O’Regan, Lan Zhao, John Wharton, David G. Kiely, Adam Kinnaird, Aristeidis E. Boukouris, Christopher W. White, Jayan Nagendran, Darren H. Freed, Stephen J. Wort, J. Simon R. Gibbs, Martin R. Wilkins - Science Translational Medicine 2017 cited by 311

that predict reduced protein function. Impaired function of these proteins causes PDK-independent mitochondrial suppression and pulmonary hypertension in mice. This first-in-human trial of a mitochondria-targeting drug in iPAH demonstrates that PDK is a druggable target and offers hemodynamic improvement in genetically susceptible patients, paving the way for novel precision medicine approaches in this disease.