Promoting myelin repair by targeting Wnt signalling
Dr David Gonsalvez, University of Melbourne was awarded a National Health and Medical Research Council / MS Research Australia Betty Cuthbert Fellowship, the MS Research Australia contribution being provided with full funding support from the Trish Multiple Sclerosis Research Foundation. The Foundation is honoured to be co-funding this important Research Project with the National Health and Medical Research Council.
· * Developing ways to repair myelin is an urgent unmet need in MS research, in the hope that new therapies might be devised that can reverse damage that has already occurred in MS and give hope to those with progressive forms of the disease.
· * Dr Gonsalvez is investigating a specific biological pathway and the ways that it might relate to myelin and myelin repair in MS.
· * Dr Gonsalvez has found that he can promote myelination via this pathway using a combination of blocking and stimulating molecules and it is hoped this might be able to repair myelin in a biological system.
· * Further studies are now planned to test this in laboratory models of MS and to look for differences in brain and spinal cord tissue under the microscope.
Progress to Date
Dr Gonsalvez has made excellent progress and has begun investigating the Wnt/B-catenin signaling pathway and its role in myelination in a normal system. He has discovered that blocking this biological pathway delays the growth and development of cells that make myelin, called oligodendrocyte precursor cells (OPCs). This prevents the OPCs from dividing to make new cells, thus decreasing the overall number of cells able to make myelin. However, Dr Gonsalvez found that this smaller number of cells were still able to make enough myelin.
Dr Gonsalvez then performed experiments to test whether blocking the Wnt/B-catenin pathway affected myelination in a laboratory model of MS. In preliminary results, they found that they could promote myelination using a combination of blocking and stimulating molecules on the Wnt/B-catenin pathway. While much remains to be tested, this implies that this combination could be used to promote myelin repair within a biological system. Research to answer this question is now underway.
At the same time, Dr Gonsalvez is also determining the role of the Wnt/B-catenin pathway in brain and spinal cord cells in humans. To achieve this he has learnt a new technique called Spectral Reflectance Confocal Microscopy imaging. He will now use this technique to measure the myelination levels in the brain and spinal cord.
This work has been presented at national and international conferences and Dr Gonsalvex has won multiple travel grants which will allow him to attend these scientific meetings. Dr Gonsalvez has also received a grant from the Department of Anatomy and Neuroscience for a $10,000 microscopy lens which will allow him to accelerate his observations of the myelin repair.
This work has the potential to identify new therapeutic target that promote myelin regrowth and slow the progression of MS.
· Gonsalvez et al., The roles of extracellular related-kinases 1 and 2 signalling in CNS myelination. Neuropharmacology (2016) 110, Part B, 586-593
· Gonsalvez et al., A Brain-Derived Neurotrophic Factor-Based p75NTR Peptide Mimetic Ameliorates Experimental Autoimmune Neuritis Induced Axonal Pathology and Demyelination. eNeuro (2017) 4 (3) ENEURO.0142-17.2017