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MS is an autoimmune-driven neurological disease. Whilst a number of treatment options exist, none of them are able to cure the disease. To overcome this bottleneck new therapies are required.
Dr Christopher Siatskas’ research will combine novel immune regeneration and gene therapy approaches, aimed at purging culprit autoimmune cells that are responsible for the development of MS.
A rational approach for the treatment and cure of autoimmune diseases such as MS requires incorporation of three fundamental processes: suppression of the inflammatory response, restoration of the immune system’s tolerance to self (“self-tolerance”) and regeneration of the target cells or tissues. Current clinical practice at best addresses the first problem but there are no clear strategies for the other two.
Given that all available treatments for MS offers patients only partial relief from symptoms, the significance of these regenerative and gene therapy-based approach to re-establish immune tolerance provides a genuine opportunity to develop a more targeted strategy to permanently eliminate rogue immune cells that are at the fulcrum of the pathogenic process and reverse autoimmune disease.
This research will also elucidate cellular mechanisms used to establish tolerance, which may offer new insight into the disease process. The results will provide important information that may be translated into the clinic.
Dr Siatskas has previously established a novel method of suppressing the inflammatory response. This method was able to reduce clinical symptoms in a laboratory model of MS. Dr Siatskas is now investigating a new approach to restore self-tolerance. His approach uses 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’.
Dr Siatskas showed in a laboratory model of mice with MS-like illness, that treatment in the thymus prior to the onset of the disease reduced inflammation and neurological damage. He investigated what happens when treatment is started after clinical symptoms begin (as would be the case in human disease). Dr Siatskas targeted different protein molecules on the immune cells, comparing between young and aged mice. Aged mice are thought to be a better reflection of the human MS condition, and it is important to also study how the immune system changes with age. After very comprehensive analyses, Dr Siatskas demonstrated that treatment targeted against specific protein molecules was able to induce self-tolerance and suppress disease scores in the young animals with MS-like disease, but the aged mice did not develop tolerance or reduce disease severity.
This work shows that promoting tolerance mechanisms in young mice can limit disease progression, but that the aged immune system presented a significant barrier to achieve immune tolerance. This important work suggests that new treatment options are needed that are effective for aged mice with MS-like disease that more accurately mimic the human condition. This work has resulted in three publications in medical journals, with another two underway (please see below for details).
Updated: 30 June 2014
$290,000
2011
3 years
Past project
