Major Research Interests
We pursue a basic research interest in glia cell biology, axon-glia interaction and mechanisms of diseases of the peripheral nervous system (PNS). We have generated a transgenic rat model of the most frequent human neuropathy, Charcot-Marie-Tooth disease type 1A (CMT1A). This disease is associated with a partial duplication of chromosome 17 which leads to an overexpression of the tetraspan protein PMP22. Transgenic "CMT rats" expressing additional copies of this gene share characteristic clinical features of the human disease, including muscle weakness, reduced nerve conduction velocities, and marked Schwann cell hypertrophy resulting in onion bulb formation. The CMT rat allows a better understanding of the cellular disease mechanism operating in human CMT1A, and is helpful in the analysis of modifier genes, epigenetic factors, and in the evaluation of experimental treatment strategies. In an attempt to translate findings from the animal model to humans we have recently identified biomarkers of disease severity in CMT1A patients. We are currently validating markers in patients from across Europe which should help us to perform clinical trials in the near future.
Homepage Department/Research Group
Selected Recent Publications
Zeb2 is essential for Schwann cell differentiation, myelination and nerve repair.
Nat Neurosci.; 19(8):1050-9. doi: 10.1038/nn.4321. Epub 2016 Jun 13.
Curcumin therapy in a Plp1 transgenic mouse model of Pelizaeus-Merzbacher disease. Ann Clin Transl Neurol. 2, 787-796
The role of combined SNV and CNV burden in patients with distal symmetric polyneuropathy. Genet Med.;18(5):443-51. doi: 10.1038/gim.2015.124.
Progesterone Antagonist Therapy in a Pelizaeus-Merzbacher Mouse Model.
Am J Hum Genet. 94, 533-546
Selected items from the Charcot-Marie-Tooth (CMT) Neuropathy Score and secondary clinical outcome measures serve as sensitive clinical markers of disease severity in CMT1A patients.
Neuromuscul Disord. 24, 1003-1017
Soluble neuregulin-1 modulates disease pathogenesis in rodent models of Charcot-Marie-Tooth disease 1A.
Nat Med. 20, 1055-1061
A rat model of Charcot-Marie-Tooth disease 1A recapitulates disease variability and supplies biomarkers of axonal loss in patients.
Brain 135, 72-87
Murine therapeutic models for Charcot-Marie-Tooth (CMT) disease.
Br Med Bull. 102, 89-113