Elizabeth CM de Lange, PhD, Leiden University, Netherlands
Editorial Board Member
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Prof. Elizabeth de Lange (PhD, PharmDhc) is staff member at the Division of Systems Biomedicine Pharmacology of the Leiden Academic Center for Drug Research (LACDR) and PI of the Predictive Pharmacology research group. She has been trained as a Biophysical Chemist and had her PhD in Pharmacology on “The use of microdialysis to study drug transport across the blood-brain barrier in health and disease”.
Liesbeth’s ultimate aim is to predict human drug effects and early neurodegenerative disease stage by translational model development on the basis of preclinical and clinical data. To that end she underscores that the rate and extent of the body (biological systems) processes are condition dependent. Therefore, the mutual coherence and time dependencies of biological systems processes should be unraveled by strategic preclinical and clinical experimentation to obtain multilevel and longitudinal data combined with mathematical modelling (Mastermind Research Approach).
As the pharmacokinetics (PK) and pharmacodynamics (PD) of a drug are dependent on the interaction of the drug with the biological system, it depends on drug properties and rate and extent of biological systems processes. It is actually the understanding of the differences in the rate and extent of those processes between biological systems that forms the basis for interspecies and condition translation and prediction. Her research focusses on measurement of the PK of the drug in plasma; drug transport into and out of the target tissue; drug distribution within the target tissue; drug equilibration to the target site; and the ability of the drug to interact with the target, and (biomarkers of) the drug’s PD. These are interdependent. Particular emphasis lies on investigations on drug distribution to target tissues protected by special barriers, like the brain. A recent success has been the development of a physiologically-based multi-CNS compartment model that adequately predicts the PK of drugs in the different compartments of the mouse, rat and human CNS, only using the physico-chemical and biological properties of the drug.
As neurodegenerative diseases develop over time. For Alzheimer’s disease there is a lack of understanding on what makes the systems processes change in the onset of the disease, and how processes interact in disease progression. Especially the information on what causes the onset and early disease progression is important for developing intervening drugs before irreversible changes will dominate, to halt or even reverse the disease progression. Also here, the Mastermind Research Approach is applied, by measuring different endogenous compounds at different locations in preclinical species (including blood, Brain sites, CSF etc), at different stages in life. This will be translated to the human situation, and lay the foundation for a blood derived biomarker fingerprint, which is more patient friendly manner of a diagnose compared to a lumbar puncture for measuring in the cerebrospinal fluid (CSF), or (expensive) imaging modalities. Especially, a blood derived biomarker fingerprint of early stage AD would be of added value.