Enhancing Myelin Repair in MS

Professor Trevor Kilpatrick

Florey Institute of Neuroscience and Mental Health, VIC

January 2018

specialisation: Neurobiology

focus area: A cure via repair and regeneration

funding type: Project

project type: Investigator Led Research

Summary

In MS, myelin, the protective coating around the nerve cells in the brain and spinal cord is damaged by the immune system. This coating not only protects nerves but also provides nourishment and support, and without it nerve cells will eventually die. Current MS therapies suppress the immune system but do not promote the repair of nerve cells which have been previously damaged.

Professor Trevor Kilpatrick and his team are investigating a protein called Tyro3 which in the laboratory has been shown to improve the natural repair processes in the brain by causing the production of myelin. In this project, this team will determine whether producing more myelin in laboratory models of MS is enough to reverse the damage associated with MS. They will also test if certain other medications, already approved for treating other diseases, (in what is known as drug repurposing) are able to promote new myelin production in the brain in a laboratory model of MS.

These studies could lead to the creation of new therapies or repurposing of current therapies to enhance myelin repair, and slow down or stop the progression of MS.

Progress

Professor Kilpatrick and his team have made considerable progress in deciphering the mechanisms of how the Tyro3 protein might be aiding in the remyelination process. This is an important step if medications targeting Tyro3 are going to be developed and used to enhance remyelination in people with MS.

They have made some important findings that will inform how and when we could use any therapies aimed at activating Tyro3. In addition to focusing on the brain and spinal cord, they are also focusing on parts of the visual system, which is severely impacted in the absence of Tyro3. Professor Kilpatrick and his team’s research suggests that Tyro3 plays an important role either in neuronal health or the connections between different neurons within the visual system. They also found that loss of Tyro3 is linked to a loss of a certain type of neuron in the retina called retinal ganglion cells and affects the structure of these cells. These important findings uncover a previously unknown role of Tyro3 in the retina, and strongly suggests its action in neurons may be part of the therapeutic effect of another protein called Gas6, which binds to Tyro3.

Professor Kilpatrick and his team have also looked at the structure of myelin in the absence of Tyro3 and found that it was significantly thinner and there were substantial disruptions to the region where the myelin meets the nerve. Mathematical modelling of these structural changes predicts that the absence of Tyro3 would cause reduction in messages between the brain and other parts of the body. These findings highlight the importance of thoroughly looking at the effects of structural changes to myelin, which has relevance to outcome measures of clinical trials of potential remyelination therapies in MS.

By understanding the full role of this protein in MS, we can better understand how targeting it may be beneficial as a treatment for MS. This may pave the way for the creation of new therapies, or the repurposing of current therapies approved for other diseases to enhance myelin repair to slow down or stop the progression of MS.

Professor Kilpatrick and his team have presented the results of this study at national and international conferences and have published part of these research findings in a scientific journal. They are currently in the process of publishing another manuscript in a scientific journal.

publications

  • Blades, F., Wong, V.H., Nguyen, C.T.O., Bui, B.V., Kilpatrick, T.J. and Binder, M.D. (2020) Tyro3 contributes to retinal ganglion cell function, survival and dendritic density in the mouse retina. Front. Neurosci. 14:840

Updated 31 March 2021

lead investigator

total funding

$225,000

start year

2018

duration

4 years

STATUS

Past project

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Enhancing Myelin Repair in MS