Holy Grail: Can stem cell transplant settle the question of EBV role in MS?

Multiple sclerosis

13 Mar 2023

Can you explain the aim of your project in 10 words?

Using the AHSCT model of immune depletion/reconstitution to study EBV in MS.

Numerous studies support a role for EBV in MS but the mechanism remains unknown. Why has it been so elusive?

EBV is very common, affecting 95+% of the adult population. MS is fairly rare (approx. 33,000 Australians on the last epidemiological study). Trying to fully explain how a common infection can cause MS would require an ability to study the immune system ‘in real time’ and great detail in people who are exposed to EBV and then follow these individuals, again with incredibly detailed immune phenotyping until a very small number go on to develop MS. You can imagine that would be financially and probably technically impossible. In response, we are left to retrospectively study the immune system of people with MS, which has limitations.

How does autologous haemopoietic stem cell transplant (AHSCT) help inform the EBV question?

This study attempts to get around this issue of longitudinal follow up… to a degree. We have prospectively collected blood samples from people living with MS undergoing AHSCT. This treatment acts as an ‘immune reset’; so we can see how the novel immune system reacts to infections like EBV and whether people’s MS reoccurs. It’s not a perfect model though. I’m hoping this work will point us in the right direction for future research. I’m very grateful MS Australia supports this kind of seed research.

What have you and/or your co-investigators previously discovered in this area?

We know that after AHSCT, roughly a third of patients have detectable EBV virus in their blood for the first three months post-transplant. So, we can assess the immune system of those with and without exposure to EBV. We also know that following AHSCT many patients retain T and B cell immunity to EBV. How and why that may influence their MS is what we want to look at next. [Read a recent Review article by Dr Massey and colleagues here]

What excites you most about this research?

The import of EBV in MS has been an unresolved issue for decades. This research asks why a treatment such as AHSCT, where one would assume you would see increasing incidence of viraemia and a lack of adaptive immune control against EBV, is a highly effective therapy in the prevention of inflammatory demyelination (relapses, new/active MRI lesions). Does it relate to the eradication of B cell reservoirs of EBV? Or is it more complex than that?

How long before the new research might impact patient care?

A better understanding of whether EBV is a trigger or one of many triggers of MS, versus an ongoing driver of the disease is key to MS treatment and prevention. The approach to treatment and/or prevention will differ, pending the mechanism. I’m hopeful that as a scientific community we will be able to answer this question in the next 5 years.

What’s your Holy Grail – the one thing you’d like to achieve in your research career?

I would like to look back and have the people I supervise in research say that I was a good leader and role model. I have been lucky enough to work with very inspirational, supportive and fun people. I would be satisfied with my career if people I mentor and supervise say the same thing about me.

What is your biggest research hurdle?

Probably time. My very wise PhD supervisor, who I still work closely with, frequently reminds me that you can buy everything apart from time.

Who has inspired you most in work or life?

I have been lucky enough to work with many inspirational clinicians, clinical academics and scientists. I was told many years ago that you ‘can’t have it all’; that good clinical practice, an academic interest, family, friendship, and free time can’t co-exist. The people who inspire me most are those that seem to find a way to balance the lot. Personally, my husband’s level
headedness, strong work ethic and intelligent but pragmatic approach to life is inspirational!

There’s an app for that. What’s new on your phone?
Storypark where my kids’ pre-school shares very cute pictures and updates of their day and, embarrassingly, ‘Shop which tracks the shipping on my online purchases! Nothing academic awkwardly.

Already a member?

Login to keep reading.

Email me a login link