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In MS it is the oligodendrocytes, the cells that generate the insulating myelin coat around nerve fibres, that are lost. A crucial therapeutic challenge after a de-myelinating event is to identify ways to promote re-myelination by surviving oligodendrocytes. In work previously funded by MS Research Australia see project here, Dr Xiao and her colleagues have identified that Brain Derived Neurotrophic Factor (BDNF), a growth factor protein that is found in the CNS, can enhance myelination. They have recently designed a small and stable peptide (small part of a protein) that mimics the shape of BDNF.
The team will now synthesise this small peptide and determine its potency in promoting myelination. This study is significant in that it will embrace an innovative approach to study CNS myelination, as well as provide proof of principle that agents such as this BDNF mimic-molecule can act as therapeutics to treat human demyelinating diseases such as MS.
The synthesis of the BDNF mimic-molecule, tricyclic dimeric peptide 6 (TDP6), was successfully completed. The peptide was then tested for its ability to promote myelination in a laboratory setting. Dr Xiao used an assay that utilises cells grown in the laboratory for monitoring myelin regrowth. Dr Xiao also determined the potency of the peptide and optimal concentration of the peptide for promoting myelination.
Using a genetic analysis approach, Dr Xiao then identified that the TDP6 peptide enhances myelination by selectively activating certain molecules on the surface of oligodendrocyte cells, known as TrkB receptors. Using mice in which the TrkB receptors were specifically deleted from oligodendrocytes, Dr Xiao tested the myelin promoting activity of the BDNF peptide. These findings provide a novel target for development of future therapies to repair and regenerate myelin.
Updated: 30 June 2014
Dr Junhua Xiao
Associate Professor Richard Anthony Hughes
Dr Agnes Wong
$18,100
2012
1 year
Past project
