RESEARCH AT CHDR, LEIDEN: BIOMARKER AND METHOD DEVELOPMENT TO AID PROOF OF PHARMACOLOGY STUDIES IN HEALTHY SUBJECTS AND PATIENTS
Abstract
At the Centre for Human Drug Research, a clinical pharmacology research institute in Leiden, methods and biomarkers are developed with the purpose to measure pharmacological effects in humans. These methods are used in early phase clinical drug studies aimed at proof-of-pharmacology of new drugs that are being developed by the pharmaceutical and biotechnology industry. Two examples of such studies will be given: one of a recently finished study and one of an ongoing study.
The study that was recently finished was aimed at finding a measure of the turnover rate of myelin in the central nervous system of humans. Six healthy subjects were administered deuterated water (D2O) for a period of 10 weeks. Over a period of 1.5-2 years they underwent 5 lumbar punctures at different time points. One of the breakdown products of myelin, beta-galactosylceramide, was extracted from the CSF and the increase in heavier isotopomers of this molecule was followed over time using mass spectrometry. A modeling approach yielded an expected turnover of this molecule of 413 days, which is also assumed for myelin. This method may be used in future studies to determine whether drugs that are being developed for multiple sclerosis can positively influence (re-)myelination.
The study that is still ongoing is aimed at determining whether peripheral excitability studies can be used to measure aute pharmacodynamic effects of riluzole and retigabine in patients with amyotrophic lateral sclerosis (ALS). Recent findings suggest that hyperexcitability (as a pathophysiological insult) may precede the structural damage to the motor neuronal system in ALS. Interestingly riluzole, the only registered drug for the treatment of ALS, has shown to partially normalize some hyperexcitability parameters (both peripheral and cortical) in patients with ALS. Therefore, if this phenotype can be reliably measured in patients with ALS, modulation of hyperexcitability could serve as a proof-of-pharmacology biomarker to track the effect of therapeutic interventions.
Wednesday 2 December 2015, 16:30 - 17:30 h
Building Carré - room CR 3.022 (Auditorium ECTM).