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Project Coordinator: LUMC

Leids Universitair Medisch Centrum, Leiden, The Netherlands

Prof. Ferrari is Project Director of the EUROHEAD Project at Leiden University Medical Centre (LUMC). As professor of Neurology, in particular of episodic disorders, he has a longstanding expertise in conducting clinical, epidemiological and genetic migraine research. The close collaboration with the Dept. of Human Genetics (Prof. Frants) and their expertise with genetics and animal models complements his expertise. LUMC will make its unique clinical, family and population-based material, and transgenic mouse model available to EUROHEAD research.

Summary of relevant expertise

  1. Genetics of migraine. The first gene for familial hemiplegic migraine (FHM1), a subunit for voltage-gate calcium channels was identified in Leiden in 1996. To identify genes for migraine with aura, recently a dense genome scan in a set of 150 trio's (patients and parents) originating from the genetic isolate of the Central Valley of Costa Rica was completed and yielded over 410,000 genotypes. Shared haplotype analysis is currently underway to identify diseased haplotypes.
  2. Functional analysis transgenic models. Recently, the first transgenic mouse model has been generated in Leiden that carries a pathogenic FHM mutation in the calcium channel subunit Cav2.1. Other models such as a knock out model of the same gene that also was generated in Leiden, and several natural mouse models, such as the tottering and Rolling Nagoya are being studied. Electrophysiology of the neuromuscular junction has shown that in tottering there is an increased spontaneous release of neurotransmitters, while there is an increased run down at high-frequency stimulation. The transgenic work is supported in part by a grant from the European union (5th Framework Research Training Network entitled Neuronal calcium channels in human disease").

Five recent publications: (From a total of > 250 Peer-reviewed publications)

Gene dosage-dependent transmitter release changes at neuromuscular synapses of CACNA1A R192Q knockin mice are non-progressive and do not lead to morphological changes or muscle weakness.

Kaja S, van de Ven RC, Broos LA, Veldman H, van Dijk JG, Verschuuren JJ, Frants RR, Ferrari MD, van den Maagdenberg AM, Plomp JJ

Neuroscience 2005;135:81-95.

Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine.

Dichgans M, Freilinger T, Eckstein G, Babini E, Lorenz-Depiereux B, Biskup S, Ferrari MD, Herzog J, van den Maagdenberg AM, Pusch M, Strom TM.

Lancet 2005;366:371-7

Infarcts in the posterior circulation territory in migraine. The population-based MRI CAMERA study.

Kruit MC, Launer LJ, Ferrari MD, van Buchem MA.

Brain 2005;128:2068-77.

Cardiovascular risk factors and migraine: the GEM population-based study.

Scher AI, Terwindt GM, Picavet HS, Verschuren WM, Ferrari MD, Launer LJ.

Neurology 2005;64:614-20.

A Cacna1a knockin migraine mouse model with increased susceptibility to cortical spreading depression.

van den Maagdenberg AM, Pietrobon D, Pizzorusso T, Kaja S, Broos LA, Cesetti T, van de Ven RC, Tottene A, van der Kaa J, Plomp JJ, Frants RR, Ferrari MD.

Neuron 2004;41:701-10.

This page last modified: 06/04/2006