Migraine is a neurovascular disorder, which has been ranked by the WHO as the 7th highest cause of disability in the world. Our laboratory is one of the leaders in neurovascular research on the pathophysiology and pharmacological treatment of migraine. We focus both on the therapeutic efficacy and the cardiovascular side effect profile of the drugs. In the past we have performed landmark studies in relation to the triptans (i.e., 5 HT1B/1D receptor agonists), including pharmacogenetic trials.1-3 We are currently involved in the investigation of CGRP-ergic ligands in relation to antimigraine treatment.4,5
Future antimigraine drugs are likely to be antibodies against CGRP or the CGRP receptor. In addition, glutamatergic ligands,6,7 novel formulations of 'older' antimigraine drugs,8 as well as many other targets9 are being explored. It is important to assess the potential cardiovascular effects of future drugs, since these may be clinically relevant, even for drugs that are primarily thought to act via a neuronal mechanism of action.7,9 We have an outstanding track record on preclinical neurovascular studies, in vivo as well as in vitro, on both human tissues and animals.
State-of-the-art techniques to evaluate (neuro)vascular function in vivo (telemetry, metabolic cages, ultrasound, laser Doppler flow, microCT imaging, intravital microscopy) and ex vivo (Langendorff heart preparation, Mulvany myograph), combined with a full range of biochemical and molecular-biological analyses, including epigenetic techniques,10 are available. In addition, we have access to human coronary and meningeal arteries. Recently, we have developed several models to assess trigeminovascular activity in vivo in humans. These methods include saliva measurements of CGRP under different experimental conditions,11 but also a model where trigeminal CGRP release is assessed with laser Doppler technology.12 This model can be applied to study pathophysiological mechanisms,13 but together with medical doctors from our institute we are also able to perform detailed pharmacodynamic and pharmacokinetic studies on the effects of prospective antimigraine drugs in humans.
Companies we collaborate with: