MS outcomes are very different between people, ranging from very mild, with no significant persistent disability to very severe disability after a few years. At present, the ability to predict a person’s likely MS outcome at first diagnosis is limited.
During this fellowship, Dr Jokubaitis aims to better understand who with MS is likely to have mild disease, and who could potentially develop significant disability, as this can help people with MS and their doctors to make decisions about the treatment and management of their MS.
To do this, Dr Jokubaitis will first conduct a genetic study to determine whether she can find inherited differences between people with mild and severe disease and therefore determine whether genes can predict progression of a person’s MS.
Once genetic differences are identified, the second part of the fellowship will use these differences to build statistical models to determine just how important they are in influencing the long-term outcomes compared to demographic factors (such as age and sex), clinical factors (such as an individual’s disability scores, relapse history, MRI), and treatments. This will allow Dr Jokubaitis to find out whether genes determine MS outcomes, or whether the outcomes can be modified.
The research, if successful, will offer people with recently confirmed MS a better understanding of their likely prognosis and therefore inform treatment choice - balancing benefit and risk for their individual situation and ensure that people with MS are receiving the best possible treatments and care strategy for them.
The main focus of this research is whether a person’s genetic make-up has an impact on whether they are likely to develop mild or severe MS, with a focus on relapsing-remitting MS. A number of studies have previously been published that suggest that genes could determine MS severity.
The first part of Dr Jokubaitis’ Fellowship was to see if these past findings could be replicated in a group of people with mild or severe MS, where severity was determined based on long-term follow-up. To date Of 109 previously published genetic variations thought to be associated with disease severity, Dr Jokubaitis has identified one that stands up to scrutiny.
The second aim was to run a new genetic analysis from scratch and look for new associations between a person’s genetic make-up and disease severity. Dr Jokubaitis has compared over 2,000 people with either mild or severe relapsing remitting MS using something called a genome-wide association study. Here, she has compared over 9 million regions of the human genome between these two groups. Dr Jokubaitis has been using advanced statistical methods to ensure that any observations that have been detected are real. She has now begun to look at the biological processes that are affected in people with mild MS compared to severe MS using the genetic data.
Dr Jokubaitis has also checked the disease severity of the people with MS involved in the study again, as this could have evolved over the course of the project. This is crucial to ensure that the project results are accurate.
Together, this work will hopefully shed light on whether genetic changes can influence disease outcomes, and ultimately inform treatment choice.
Dr Jokubaitis has also developed many international collaborations with world leading MS genetics researchers for this project. The samples that Dr Jokubaitis has collected from Australian patients will be used to confirm findings from her colleagues’ international studies and the international collections will act as confirmation collections for any findings from Dr Jokubaitis’ work.
Updated: 11 June 2020
Updated: 11 February, 2017