Promoting myelin repair by targeting Wnt signalling

In 2016, Dr David Gonsalvez was awarded a Betty Cuthbert Fellowship co-funded by the National Health and Medical Research Council and MS Research Australia, with the MS Research Australia contribution provided with full funding support from the Trish MS Research Foundation. The Trish Foundation was honoured to be co-funding this important Research Project with the National Health and Medical Research Council.

Current treatments for MS are focused on stopping the immune system from damaging the myelin, and this respite from the immune attack can allow some natural regrowth of myelin. However, none of these therapies directly promote myelin repair.

In older lesions, myelin repair is, in fact, inhibited by the scarring and general conditions in the lesion. Dr Gonsalvez has been investigating a particular signalling pathway (a chemical system by which cells communicate with each other) that is thought to inhibit myelin repair called the Wnt/B-catenin signalling pathway. He is interested in how this signalling affects the cells which produce myelin and determine whether blocking these signals will then promote myelin repair. This work has the potential to identify new therapeutic targets that promote myelin regrowth and slow the progression of MS.

Dr Gonsalvez has successfully generated a laboratory model where this chemical signal is specifically blocked in oligodendrocytes (the cells that make myelin) and found that this promoted the generation of myelin. This finding suggests that this approach could be used to promote myelin repair within a person.

Dr Gonsalvez has shown that Wnt/B-catenin chemical signalling is more active in human MS tissue, and this may ultimately prevent some of the cells that make myelin. These chemicals could also play a role in the immune system and maintaining the blood brain barrier. While examining their effects, Dr Gonsalvez has discovered that the immune response may be involved in the remyelination events. He is now in the process of finding out how this is contributing to remyelination.

This work has been presented at national and international conferences and Dr Gonsalvez has won multiple travel grants which will allow him to attend these scientific meetings. He is preparing a number of manuscripts for publication in scientific journals.