Mark Kotter, University of Cambridge, Cambridge, UK

Promoting CNS remyelination by inducing OPC differentiation

Funded in: 2011, 2012, 2013

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Treatments for enhancing CNS remyelination are not yet available in a clinical setting. Remyelination in the central nervous system by stimulating the differentiation of neural stem/precursor cells have been recognised as an important strategy to ameliorate the devastating consequences of a number of neurological diseases, including spinal cord injury.

The present application is based on a series of experiments demonstrating that inhibition of specific cell signalling is able to neutralise inhibitory effects of myelin associated inhibitors and induce OPC (oligodendrocyte precursor cell) differentiation. Furthermore, preliminary experiments demonstrate that the estrogen receptor and PKC inhibitor Tamoxifen is able to induce OPC differentiation in the presence of myelin associated inhibitors in vitro and that tamoxifen treatment may also be able to induce OPC differentiation in an in vivo model.

As tamoxifen is a well-established and safe clinical drug with tolerable side effects enhancing CNS remyelination with tamoxifen would be an attractive strategy that could be rapidly translated into a clinical trial.

Aim of the project is to study the effects of tamoxifen on OPC differentiation and CNS remyelination in vivo in detail.