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Feb 2017
Trish Foundation contributes to first-ever discovery
Jun 2017
Researchers funded by the Trish Foundation making great progress
Dec 2017
Announcement by NHMRC
Jan 2018
2018 Round of Funding Four new Projects announced
Jun 2018
Exciting regrowth of nerve fibres
Jun 2018
Dr Merson secures $1 million from NHMRC
Jun 2018
Findings submitted for publication
Jan 2019
New Research Projects commencing 2019 announced

Reprogramming the immune system
in MS  

Dr Christopher Siatskas, from Monash University, has for many years been researching potential methods to manipulate the immune system to reverse the damage caused by multiple sclerosis (MS). He has recently finished a three-year project grant (2011-2013) from the Trish MS Research Foundation in partnership with MS Research Australia to pursue these important research questions.  

While a number of treatment options currently exist for MS, none of them are yet able to cure the disease. To overcome this bottleneck, new therapies are required. Dr Christopher Siatskas’ research has combined novel immune regeneration and gene therapy approaches, aimed at targeting the culprit autoimmune cells that are responsible for the development of MS.

Dr Siatskas’ work investigated a new approach to restore the immune system's tolerance to self ("self-tolerance") in a laboratory model of mice with MS-like illness. His approach used a gene therapy method that directly targets the self-reacting cells in the thymus. The thymus is the organ where immune cells are trained to recognize the difference between ‘self’ cells and dangerous cells. Targeting treatment to the thymus could prevent the release into the bloodstream of the rogue immune cells that attack the ‘self’. Importantly, his worked aimed to compare these treatment strategies in both young and aged mice, to more accurately study the effects of aging on the immune system. Aged mice may be a better reflection of the human MS condition, and it is important to understand how the immune system changes with age.

His experiments tested gene therapy in combination with a specific antibody treatment targeted against several different proteins found on the surface of immune cells. Dr Siatskas demonstrated that treatments targeted against specific protein molecules were able to induce self-tolerance and suppress disease activity in the young animals with MS-like disease, but the older mice did not respond to the treatment, failing to develop self-tolerance or have any reductions in disease severity, suggesting that there may be changes in the immune system or in the brain that occur with age.

This work shows that promoting self-tolerance mechanisms in young mice can limit disease progression, but that the aged immune system presented a significant barrier to achieve immune self-tolerance. This important work suggests that, although the new treatments being studied may be effective for young mice, further study is needed to determine if and how this type of gene therapy could be used in older populations, which more accurately mimic the human condition. Dr Siatskas’ work has been extremely productive, so far resulting in five publications in medical journals, with several more underway.

Given that all available treatments for MS offers patients only partial relief from symptoms, the significance of these regenerative and gene therapy-based approaches to re-establish immune self-tolerance provides a genuine opportunity to develop a more targeted strategy to reverse autoimmune diseases such as MS. Dr Siatskas’ future research will continue to explore the interaction between aging and novel treatment options, looking for new avenues to develop therapies that can reverse the degeneration of brain tissue in MS.        

Trish Foundation & MS Research Australia Working together to find a cure for MS
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