Pulling together the threads to understand MS

Imagine a cat’s cradle – a network of threads running to and fro, crossing over and diverging again – now imagine that the clues to MS lie at the points where all the threads cross over.

Researchers in Australia and around the world are working hard to pull together huge ‘threads’ of data on the genes and the environmental factors associated with susceptibility to MS, as well as data on the behaviour of the immune system in MS, and how it responds to the current treatments for MS. Identifying the common threads between all of these factors will ultimately help to stop the disease in its tracks.

Recently a group of international researchers published a major analysis of the networks of genes that are switched on or off in people with early MS, relative to their vitamin D levels and in response to treatment with interferon-beta. Drawing in a third ‘thread’ of data, they also looked at the number of active MRI lesions in the brains of these individuals and determined the gene activity patterns that were associated with either high or low numbers of lesions. By looking at the three patterns of gene activity and how they overlapped, the researchers were able to show that vitamin D directly controls a large system of genes, regulating immune system functioning and MS lesion activity. Importantly, they also showed that the effects of interferon-beta treatment and vitamin D levels on this gene network were added together to have a larger impact on reducing MS disease activity. These findings suggest an important relationship between genes and environmental factors such as vitamin D that may work together to influence not only MS severity but also a person’s response to MS treatment.

Dr Steve Simpson Jr, a researcher at the Menzies Institute for Medical Research and currently funded by MS Research Australia, is part of another team of researchers trying to pull the threads together. Using valuable data from the Southern Tasmanian Longitudinal MS Study they have been looking at how genes, vitamin D, and aspects of diet and lifestyle impact on relapse rates and brain lesions. Most recently the team have focused on one particular gene known as WT1 that has previously been implicated in MS susceptibility. They have revealed that variations in this gene can also influence the response of the body to both sunshine and interferon-beta treatment to increase levels of vitamin D in the blood stream.These findings show that for some people, their treatment response may be optimised in certain environmental conditions.

More research is needed to continue to pull these threads together. Research around the globe is providing vital information on how existing interventions work and how genetics may ultimately be used to help choose the right therapy for an individual.

While this data supports a potential role for vitamin D in preventing and treating MS, direct evidence is still required to show that vitamin D supplementation is a safe and effective therapy, and the most appropriate doses. This is what we are trying to achieve with the MS Research Australia-funded Vitamin D MS Prevention Trial (PrevANZ) currently underway in Australia and New Zealand.



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Pulling together the threads to understand MS