Unveiling the MS energy crisis: can we power up to rescue nerves?

My name's Kellie and I'm a PhD student at the MS Research Centre in Edinburgh. My research aims to answer the question: why do some nerves in the brain die over time in people with MS - and how can we stop it?

Recently, I found unique changes in how certain nerves make enough energy to survive myelin loss – while others don’t. I believe my research matters to all people with MS.

If we can find a way to save nerves from dying after myelin loss, we can slow disability progression in people with MS – improving quality of life.

An 'energy crisis' in nerves?

In MS, nerves lose their insulating coating of myelin, leaving them exposed and vulnerable. Myelin keeps nerves energy efficient and supplies nutrients, so they can send signals around the brain quickly.

When myelin is lost, nerves must work even harder to carry out their important energy-demanding jobs. An ‘energy crisis’ develops where there's a gap between energy needed to survive, versus the energy they can make.

Over time, this can lead to the loss of these nerves, called ‘neurodegeneration’. Neurodegeneration leads to irreversible disability, which we want to prevent for people with MS.

Damaged powerhouses in MS

So, what's responsible for providing this crucial energy supply? It's small ‘powerhouses’ in every cell in our body, called mitochondria, that make this energy. Under normal conditions, they'll turn nutrients from your food into valuable energy.

With myelin loss, the mitochondria in nerves become damaged while trying to make a lot of energy under stressful conditions.

Damaged mitochondria have been found in some people with MS and in animals with an MS-like condition. We think this might be related to important symptoms of MS – like fatigue.

Why are some nerves more vulnerable?

My research focuses on these powerhouses where myelin loss is associated with worsening disability in people with MS. 

In MS, some nerves are more vulnerable than others – why? Maybe these vulnerable nerves lack enough energy to survive or have too many stressed powerhouses, like overheating batteries?

I work with mice with an MS-like condition, so I can study the early stages of myelin loss. I use lots of exciting techniques in the lab to answer these questions. I perform a technique called ‘staining’, where I add coloured dyes to label certain proteins, like myelin. 

Using this technique, I look at the tiny powerhouses in nerves with powerful microscopes – with some beautiful images as a result! I’m also doing some cutting-edge experiments, where I can look at over 1,000 different gene copies (DNA used to make a protein) at once. This way, I can find what energy-making genes are changing right after myelin is lost. This technique is very new, so I’m excited about what discoveries may come from it!

Looking towards the future

My research will improve our understanding of how these powerhouses affect nerve loss and symptoms like fatigue in people with MS. I believe my work may identify new ways to slow worsening of disability in people with MS. Next, I'll be running a drug trial that targets these powerhouses to rescue nerves in mice with an MS-like condition. Some of these drugs, like pioglitazone, are already being trialled in people with MS. Overall, my research aims to understand why certain nerves die, to find ways to stop nerve death. To ultimately improve quality of life for people with MS.