Enhancing brain activity to re-wrap nerve fibres - MS Research Australia

Enhancing brain activity to re-wrap nerve fibres

Dr Kaylene Young

Menzies Institute for Medical Research, TAS

| 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. Myelin can be repaired, but in the progressive forms of MS, repair is not complete leading to irreversible disability. There are currently no treatment options that are capable of repairing myelin damage for people with progressive MS.

Dr Young and her team have recently established that a non-invasive technique, known as repetitive transcranial magnetic stimulation, is able to massage brain activity and increase the production of cells that produce myelin in the brain. In this project, Dr Young will use this technology as a treatment in two different laboratory models of MS. She will test its ability to increase the production of the myelin producing cells, to re-wrap nerve fibres in myelin and promote lesion repair in the brain. Dr Young will examine brain tissue under the microscope to determine effectiveness of this treatment in mediating successful repair of myelin and in combating disease progression in the models.

This type of magnetic stimulation is safe for human use and is already being used clinically for the treatment of other nervous system disorders. Therefore, it is hoped that a successful outcome from this project will allow it to be trialled in hospitals for the treatment of people with MS within a short time frame, providing a much needed therapeutic option for progressive MS.

Progress to Date

Over the course of this project, Dr Young and her team aim to examine whether transcranial magnetic stimulation can induce cells to lay down new myelin and repair existing damage in two laboratory models of MS. One model has a single small focal lesion and the other is a model of inflammatory MS.

Dr Young has carried out the transcranial magnetic stimulation on the models that have the single lesion, a large brain lesion with low-level inflammation and a large brain lesion with high-level inflammation. The last model is newly established for inflammatory MS that produces brain lesions in addition to spinal lesions. This means that it more closely resembles the pattern of lesions and myelin loss seen in people with MS. Tissues from those that received the stimulation are being compared to untreated tissue under the microscope.

Tissue preparation is now complete and analysis is underway to determine the number of new myelin producing cells within the lesion site and the amount and length of myelin that is generated in response to the magnetic stimulation. In the preliminary findings, Dr Young has found that in the single small focal lesion model, the amount and length of myelin did not change in response to transcranial magnetic stimulation. She also found that this model did not experience outward symptoms of MS and that precursors to myelin are detected at the remyelinating site. Dr Young is currently analysing the inflammatory models.

In an important step to be able to use transcranial magnetic stimulation in people with MS, Dr Young has also determined the optimal transcranial magnetic stimulation method that could be successfully translated to use in clinical trials.

It is hoped that if these experiments are successful, the transcranial magnetic stimulation may be used as a therapy to repair existing damage in progressive MS and proceed to clinical trials.

Dr Young has received funding from the Ian Potter Foundation to purchase two new confocal microscopes that will double imaging capacity. She was also successful in receiving a collaborative NHMRC grant where she will help investigate the mechanism by which myelinating cells die with the aim of designing a treatment.

Publications

  • Cullen CL, Senesi M, Tang AD, Clutterbuck MT, Auderset L, O’Rourke ME, Rodger J and Young KM (2019). Low intensity transcranial magnetic stimulation promotes the survival and maturation of newborn oligodendrocytes in the adult mouse brain. Glia. 67:1462-1477
  • Pepper RE, Pitman KA, Cullen CL, Young KM (2018). How Do Cells of the Oligodendrocyte Lineage Affect Neuronal Circuits to Influence Motor Function, Memory and Mood? Front Cell Neurosci. 12:399

Updated: 31 March 2019

Updated: 03 March, 2017

Investigator

Co-investigator

Grant Awarded

  • Project Grant

Total Funding

  • $170,000

Duration

  • 3 years over 2017 - 2019

Funding Partner

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