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MS results from the loss of myelin, the insulating sheath around nerve fibres, in the brain and spinal cord. Brain-derived neurotrophic factor (BDNF) is one of the proteins that controls the growth of myelin during development and is also able to repair myelin after it has been damaged. As such, BDNF could form the basis of a new treatment option to repair myelin in MS. However, since BDNF is a large protein and is broken down by the body very quickly, it cannot itself be used directly as a treatment.
In an attempt to overcome these limitations, Associate Professor Hughes and his team are developing smaller molecules which mimic the function of BDNF but might also be suitable as therapies. Associate Professor Hughes and his team were previously funded by an MS Research Australia Incubator Grant to develop a synthesis method for a compound called ‘TDP6’, which mimics BDNF and is able to repair myelin.
This project is further investigating the precise way that this new compound repairs myelin and also determining the chemical and pharmacological profile of this potential drug, important further steps in turning TDP6 into a drug for treatment. They also plan to make improvements to the current TDP6 design which will make the compound smaller and more potent. The team will also develop other mimics of BDNF for further investigation as a treatment option for MS.
Repair of myelin damage is the holy grail of MS research, as treatments which promote repair would be able to restore function that has been lost and provide therapeutic options for people with progressive forms of the disease.
Associate Professor Hughes and his team have redesigned the TDP6 molecule to improve its structure. Using a cutting-edge chemistry technique in a completely new way, they substituted some of the molecular components of the compound with more efficient chemical connections. This will make this version of TDP6 more effective as a treatment for MS and will considerably refine and simplify the way it is made, an important consideration if it is to be scaled up as a therapy for MS.
Associate Professor Hughes has made seven versions of TPD6 with different molecular components and has carried out many experiments to determine the optimal conditions for the reaction. He has begun comparing the actions of these new versions of the drug to the original form in different biological pathways, including their ability to remyelinate.
Since this is a completely novel use of the chemistry, Associate Professor Hughes and his team have thoroughly investigated the chemical reactions and have also published this work in a scientific journal. This work has also been presented at national conferences and has underpinned a PhD project and formed part of the work undertaken by a postdoctoral researcher.
Updated: 11 June 2020
Associate Professor Richard Hughes
$165,000
2017
4 years
Past project
