Holy Grail: can a brain-derived neurotrophic factor (BDNF) mimetic promote myelin repair?

Movement disorders

9 May 2019

What inspired you to get involved in MS research?

Circumstance and good mentoring! Just out of my PhD, I landed a postdoc in New York that was interested in Schwann cells – the cells that produce myelin in the peripheral nervous system – and I just fell in love with them. Great to culture, amenable to manipulation, good biochemical readouts and express a really good suite of molecules to investigate. When I returned to Australia, I was offered the sagely mentoring advice to consider moving my research into the brain and work on the cells that produce myelin in the central nervous system – oligodendrocytes. And I haven’t looked back since

What do you think has been the most exciting development in MS research

Our brains have an amazing endogenous capacity to repair myelin. However, in MS, this capacity is less effective and over time doesn’t work at all. I think the most exciting development in MS research is the focus on myelin repair – in particular with 4 clinical trials underway! This is an exciting time; but I hope this is just the tip of the iceberg, with more research developing new molecules and new strategies to promote myelin repair. Each grant, discovery and publication offers a new opportunity to develop a treatment for myelin repair that could ultimately help everyone with MS.

Tell us about your current research project?

One of the major issues in MS is that the brain’s capacity to repair myelin, the tissue that is affected in this disease, is limited. We have developed a strategy that does promote myelin repair, but in young animals where the normal capacity for myelin repair is high. This research project is focussed on a more complex model where myelin repair does not normally occur. This research will help identify whether our strategy is a rational approach that could cure MS.

Why is your research important and how will it influence the understanding and treatment of MS?

We pioneered work that identified that the neurotrophin brain-derived neurotrophic factor (BDNF) promotes myelination during development, acting directly on the myelin producing cells called oligodendrocytes. This led us to the view that BDNF might also promote myelin repair after injury, such as occurs in MS. In collaboration with others, we developed a drug-like mimetic of BDNF and identified that it indeed could promote myelin repair in a mouse model of central demyelination. However, these studies were executed in a permissive environment, where spontaneous remyelination occurs – in relatively young animals after a single bout of demyelination. This is not the environment in which myelin repair must occur in multiple sclerosis – in a more mature nervous system that has a less permissive environment. The innovative aspect of this study is that we have manipulated the experimental model to include repeated bouts of demyelination in older mice to develop a demyelinated environment that does not spontaneously remyelinate. This adaptation more closely approximates the environment in which remyelination must occur in multiple sclerosis. Examining the efficacy of our BDNF mimetic in this environment is a small but significant step towards identifying whether this is a rational approach to cure MS.

What do you enjoy most about working in the lab and what are some of the challenges you face?

How many people get to go to work and discover something completely new? The lab is a great place to be – planning, designing and executing experiments to discover new knowledge, something no one has ever seen or heard of before. But that’s not the best bit – the prospect that one day one of your discoveries will help people is just awesome. Just like sands through the hourglass……my biggest challenge is time – I find the time it takes to execute and analyse a thoughtful and well-planned experiment very frustrating. I just want the results straight away, so I can move on to the next idea and experiment.

Tell us an interesting fact about yourself …

When I’m not in the lab or thinking about science, I’m normally planning my next camping trip out to somewhere remote in my 4WD. Either that, or I’m in the aisles at ALDI checking out the special buys of the week.

This article was originally published by MS Research Australia

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