Biomarker development for new drug targets to improve the efficiency of early clinical drug development: focus on TRP channels. - Belgium
- The human genome encodes several hundreds of ion channels, with strongly divergent gating properties and physiological roles.
- Acquired or inherited malfunctioning of these ion channels can cause many diseases including: cystic fibrosis, cardiac arrhythmias and neuropathic pain.
- Therefore, ion channels are prime targets for drug therapies.
- This project focuses on the superfamily of TRP channels. TRP channels, classified into 6 subfamilies, belong to a large group of stimulus detectors gated by physical stimuli as well as various endogenous and exogenous ligands. As TRP channels play an essential role in many physiological processes, dysregulation can result in severe human pathologies. Consequently, TRP channels are amongst the most pursued targets in drug development.
- However, the translation into the clinic of efficacy seen in preclinical animal models with these drugs is problematic. In addition, due to increasing costs in clinical drug development, there is an urgent need for target-engagement biomarkers as a first indication of potential efficacy in humans.
- The main objective of this project is to develop target-engagement biomarkers for TRPM receptors in general in order to improve early clinical drug development and to gain insight in the role of these receptors in pathophysiology. Given the key role of TRPM3 in acute and chronic pain models, specific aims are to:
- delineate the contribution of TRPM3 to clinically relevant forms of chronic pain,
- identify the mechanisms whereby TRPM3 regulates hypersensitivity and pain, and (3) develop an assay to assess TRPM3 activity in humans.
- The PhD candidate will first develop and validate models for TRP channel activation in healthy volunteers in terms of reproducibility.
- Secondly, these models will be applied in specific patient populations to gain insight in the contribution of these channels to human pathophysiology.
- Finally, where possible, the models will be applied as target-engagement models in early clinical drug development.
- We are looking for a highly motivated candidate holding a Master in Medicine, Biomedical Sciences or Pharmaceutical Sciences.
- Knowledge of clinical drug development and basic skills in clinical research are an added value but not mandatory.
- Project duration: 4 years
- This project involves clinical studies in healthy volunteers as well as in patients