Myelin repair - from lab discoveries to clinical impact
On 6 June, Professor Thóra Káradóttir gave our ninth Stop MS Annual Lecture. Thóra is co-lead of our MS Society Cambridge Centre for Myelin Repair. Here are just some of the things we learned in her lecture.
1. Our nerves share similarities with deep sea cables
Thóra likened our nerves to the transatlantic telecommunication cables between London and New York. To get a fast and reliable signal, they needed to install a multi-layered insulation. In the same way, a fatty substance called myelin forms a sleeve around the ‘cable’ section of our nerves, known as the axon. It allows fast communication between nerves and protects them from damage. But in MS, myelin gets damaged, disrupting communication and causing symptoms.
2. Myelin can be repaired... but this doesn't always work
Immune cells can clean up damaged myelin. And stem cells transform into special cells called oligodendrocytes to repair it. Early in MS, this process works quite well, and MS symptoms may lessen or go away.
But this process isn’t fail-safe. As we age and as MS progresses, it can stop working as effectively. When this happens, nerve cells can be lost, and symptoms become permanent. Thóra explained that evidence is mounting that this can also lead to something called ‘smouldering neuroinflammation’. This is a low-level brain inflammation that can damage tissue over time and drive MS progression.
3. Inflammation isn’t always bad
Our brains are made up of grey matter and white matter. Grey matter is the computing part of the brain, responsible for processing and interpreting information. White matter is made up of nerve fibres that allow different parts of the brain to communicate with each other. Myelin gives white matter its colour.
By studying animals, researchers discovered a wave of inflammation in the brain’s grey matter during myelin repair. Although we often think of inflammation as ‘bad’, here it seems to be a helpful part of the process.
When the team stopped myelin from repairing in these animals, the brain inflammation remained high. It looks like this might be mirroring what we see with the smouldering neuroinflammation that leads to MS progression.
4. Age is important
Ageing is the biggest risk factor for failure of myelin repair. The team found that older animals had higher levels of inflammation even before their myelin was damaged. So the delicate balance of inflammation and repair was disrupted.
Previous work at the Cambridge Centre showed that the diabetes drug metformin seems to rejuvenate brain stem cells, improving myelin repair in older animals. Thóra shared some early results showing that metformin also reduces brain inflammation in these older animals.
5. Researchers are testing myelin repair drugs in trials
Thóra highlighted the need for a range of treatments that can:
- stop attacks by the immune system
- maintain the right balance of inflammation
- promote myelin repair
- protect nerve cells
Researchers at the Cambridge Centre are involved in trials for myelin repair treatments.
Their trial of bexarotene was the first to show that it is possible to promote myelin repair in people with MS. Harsh side-effects meant that it wasn’t suitable for people with MS to use in this way. But this autumn, the team will start a new trial testing bexarotene again. This time at a lower dose and alongside another drug.
They're also running a trial of metformin and clemastine. This combination is being tested in a phase 2 trial, based on evidence that clemastine triggers myelin repair and metformin boosts its effect.
[Photo of Professor Thóra Káradóttir, credit: Alun Callender]
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