Interferon-beta (IFN-β) was the first specific disease-modifying therapy approved for MS and remains one of the most commonly prescribed MS treatments worldwide. Clinical trials of IFN-β treatment in people with MS have demonstrated that this treatment provides both a reduction in the relapse rate and in lesion number on brain imaging. Despite these benefits, not all MS patients respond well to IFN-β treatment, particularly those who may be in a more active phase of the disease, and many people also experience significant side effects.
These side effects are due to the IFN-β treatment having effects on a large number of genes, not all of which are related to the way IFN-β acts to treat MS. One such gene makes a molecule that regulates the activity of other genes, known as pS-STAT1. Little is known about this molecule, although past studies have shown that it may play a role in the progression and exacerbation of MS.
Dr Hofer will investigate pS-STAT1 within the brain and spinal cord of a laboratory model of MS and also chart the activity of pS-STAT1 in brain tissue from people with MS. This pilot study will determine whether pS-STAT1 represents a promising target for developing novel therapeutics that improve the efficacy and tolerability of IFN-β treatment for people with MS.
Emerging evidence suggests pS-STAT1 may play a role in MS disease progression. Low levels of ps-STAT1 gene activity have been linked to a reduced effectiveness of the IFN-β treatment. However, little is known about pS-STAT1 in the brain. This pilot project aimed to discover more information about the role of pS-STAT1 in the brain in a laboratory model of MS.
Dr Hofer and his team discovered a link between pS-STAT1 and the amount of inflammation and tissue damage in the brain in this model. They are currently writing up this finding for publication and determining how pS-STAT1 modulates the response of immune cells to IFN-β.
These result demonstrate that pS-STAT1 may play an important role in mediating the effects of IFN-β in the central nervous system, and that it may be a promising target for developing novel therapeutics.
To confirm this, Dr Hofer and his team are now optimising protocols for detecting pS-STAT1 in human post-mortem brain tissues, and plan to continue this work through 2017. This will allow them to confirm the role of pS-STAT1 in human MS and its relationship to lesions and tissue damage.
This funding has also allowed Dr Hofer to contribute to the training of a number of young researchers, with the results from this study forming the basis of one Honours and one PhD Degree thesis. The results have also been presented at an international conference.
Updated: 17 July 2017
Updated: 04 January, 2015