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Australians develop promising

technique for Myelin repair

19 July, 2018

*  .Repairing damaged myelin is essential to prevent the progression of clinical disability in MS and techniques that promote repair are a huge unmet need in MS. 

*  Researchers based in Melbourne and funded by MS Research Australia have developed a synthetic molecule called TDP6 that mimics a natural brain protein.

*  Giving TDP6 as a treatment after myelin damage increased the number of myelinated nerve fibres and increased myelin thickness, indicating that the myelin had been repaired.

*  It is hoped that this could form the basis of new therapies to repair myelin in MS. 

The ability to repair damage that has already occurred in MS is one of the most pressing goals of MS research. In MS, the myelin coating around nerve fibres is damaged by the immune system, exposing the underlying nerve and interrupting the nerve signals travelling between the brain and the body. Current treatments for relapsing MS aim to reduce the damage caused by the immune system, but treatments that are able to repair damage are lacking.

Myelin can be naturally repaired and it is this process which leads to recovery from relapse symptoms in people with relapsing-remitting MS. However, this repair is often incomplete and eventually fails completely, leading to accumulation of progressive disability. Stimulating and enhancing the natural repair processes is a goal of many MS researchers.

A group of researchers from the University of Melbourne, funded by MS Research Australia with the generous support from The Trish MS Research Foundation, the MS Angels and the Pierce Armstrong Foundation, have been working on identifying ways to promote the natural repair of myelin damage in the brain. 

Dr Jessica Fletcher received a postdoctoral fellowship to examine the mechanisms of myelin repair at a molecular level. Working with her colleagues, Dr Simon Murray, Dr Junhua Xiao and Associate Professor Richard Hughes their new research has led to the development of a synthetic protein, which mimics a naturally occurring brain protein to promote myelin repair. 

Brain-derived neurotrophic factor (BNDF) is a naturally occurring protein in the brain that has many functions, including enhancing myelin repair. However, the use of BDNF itself as a way to repair myelin in MS has not worked for a range of reasons, including its large size and inability to efficiently gain access to the brain when given as a drug. This led the researchers to develop smaller synthetic molecules that share characteristics with BDNF, in the hope that these molecules could be used to trigger the same biological pathways that BDNF uses to enhance myelin repair.

Published online via the scientific repository BioRxiv, the study shows the synthetic protein TDP6 is able to initiate myelin repair in a laboratory model of MS. Given as a treatment after myelin is damaged, TDP6 increased the number of mature myelin-producing cells in the brain. The team were also able to show that it repaired myelin, in that the number of myelinated nerve fibres increased and myelin thickness improved after the synthetic protein was given. 

The researchers also examined the biological pathways that TDP6 used for this repair. They showed no changes in inflammatory cells in the brain, showing that the effect of TDP6 is not relying on anti-inflammatory pathways. Instead, it seems that it is acting directly on the myelin-producing cells to enhance their repair activities. 

This work has shown that this synthetic molecule can repair myelin in a biological model of MS. While more work is needed in the laboratory to develop the treatment further, it is hoped that this molecule could form the basis of a new therapy for repair of existing damage in people with MS, and provide treatment options for people in the progressive phase of their MS.

Article adapted from MS Research Australia

 

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