Investigating novel molecular targets
for promoting remyelination in the brain
Dr Jessica Fletcher, funded by an MS Research Australia Postdoctoral Fellowship, with the support of the Trish MS Research Foundation, has been working with Dr Simon Murray and Dr Junhua Xiao at The University of Melbourne, investigating novel molecular targets for promoting remyelination in the brain.
Myelin coats the nerve cells in the brain and spinal cord. In MS there is damage to the myelin, and in the early stages of the disease there is some ability to repair the myelin, a process known as remyelination. Over time the body’s ability to remyelinate becomes impaired, leading to incomplete repair and contributing to the progression of MS symptoms. It is crucial to identify potential new treatment targets that can promote myelin repair, prevent nerve damage and halt MS disease progression.
Dr Fletcher has been working on a nerve growth factor, known as brain-derived neurotrophic factor (BDNF), which has been found to promote myelination by activating different receptors, or docking stations, on the surface of myelin-producing cells (known as oligodendrocytes). BDNF is known to function alongside a number of other specific chemicals (including Erk1/2) and so Dr Fletcher is using a laboratory model of MS-like illness, to see whether the Erk chemicals in this pathway can work together to increase myelin production after activation with BDNF.
Dr Fletcher has made significant progress in her research. She has found that when a laboratory model of MS was given BDNF, Erk1/2 was activated at higher than expected levels. In turn, this appears to enhance myelin repair, as at the same time, she discovered that more nerve cells were myelinated, and had a thicker myelin sheath. She is now performing experiments to determine which cells in the CNS are responding to these signals to activate remyelination – oligodendrocytes themselves or their ‘stem cells’ the oligodendrocyte precursor cells, or whether another type of cell is involved. This research should be submitted for publication later this year, and has already been presented at national and international seminars and conferences.
To identify targets for future therapies, Dr Fletcher is learning what other molecules might be involved in the activity of Erk1/2. This year she will focus on identifying the effect of slightly changing the structure of these molecules to determine if they could be potential targets for future therapies to promote myelin repair in MS.
As a result of her work so far, Dr Fletcher has also secured further grants from the Ian Potter Foundation, and The University of Melbourne. She is also developing her career and contributing to the development of other future MS researchers by contributing to the supervision of multiple student research projects.