Designing new drugs to treat MS

Associate Professor Richard Hughes

The University of Melbourne, VIC

| A cure via repair and regeneration | Epidemiology | Genetics | Neurobiology | Project | 2017 | Investigator Led Research |
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Summary

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 will further investigate the precise way that TDP6 repairs myelin and also determine 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.

Progress to Date

Associate Professor Hughes and his team have begun work on the first aim of this research project, to improve the structure of TDP6 to make it smaller and more effective as a therapy for MS. They have refined the synthesis process for TDP6 and have substituted some of the molecular components of the compound with more efficient chemical connections.

The team has also developed a scaled-back version of the TDP6 that can be used in other experiments to test the way that the compound interacts with the other molecules and to determine which parts of the TDP6 structure are important for its function.

Analysis is also underway on the second part of the project that will attempt to improve the uptake of TDP6 in the body, an important consideration for its efficiency as a therapy. These experiments will determine the ability of TDP6 to pass through cellular membranes.

On the back of this funding, Associate Professor Hughes has established a collaboration with an industry partner to produce some of the molecules required for further testing of TDP6.

Publications

  • Fletcher JL, Wood RJ, Nguyen J, Norman EML, Jun CMK, Prawdiuk AR, Biemond M, Nguyen HTH, Northfield SE, Hughes RA, Gonsalvez DG, Xiao J & Murray SS. “Targeting TrkB with a brain-derived neurotrophic factor mimetic promotes myelin repair in the brain.” bioRxiv, 268300

Updated: 20 April 2018

Updated: 05 March, 2017

Investigator

Co-investigator

Grant Awarded

  • Project Grant

Total Funding

  • $165,000

Duration

  • 3 years over 2017 - 2019

Funding Partner

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