Reprogramming the immune system
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
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.