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 TDP6 repairs myelin and also determining the chemical and pharmacological profile of TDP6, 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 and using it 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 a more effective as a treatment for MS and also considerably refine and simplify the synthesis process for TDP6, an important consideration if it is to be scaled up as a therapy for MS. In addition to the design and synthesis, tests are being undertaken to compare the actions of the new versions of TDP6 in biological pathways and compare them to the original.
Since this is a completely novel use of the chemistry, follow up work is now underway to determine the details of the chemical reaction for the scientific community, so that this technique can be used by other medicinal chemists for other applications outside of MS.
The work has underpinned a PhD project and formed part of the work undertaken by two postdoctoral researchers. This research was also leveraged to acquire a grant for $250,000 for equipment that is needed to produce and purify the peptides used in these experiments.
Updated: 31 March 2019
Updated: 05 March, 2017