The myelin repair race is on
It’s no secret that myelin repair is a hot topic in the world of MS research right now. And so it should be.
Myelin is the protective coating that surrounds nerves - a bit like the insulation on an electrical wire. It is there to help the messages travel smoothly and efficiently down our nerves. Without it, parts of the nerve can become uncovered and vulnerable to damage.
Unfortunately, this is exactly what happens in MS. When the immune system attacks the myelin, it is stripped away from the nerve leaving it unprotected. Once exposed, nerves can become damaged causing messages being transmitted around the central nervous system to be disrupted. It is this disruption that translates into the symptoms people with MS are all too familiar with. These can be far ranging, depending on where the myelin attack has occurred and therefore which nerves in the central nervous system have become damaged.
It’s not surprising, given the importance of this fatty substance that the body has equipped itself with the ability to repair damaged myelin. This process relies on an army of myelin producing cells in the brain doing their job. These cells are called oligodendrocytes and it seems that in MS this army becomes rather depleted, limiting the natural process of myelin repair.
So the theory amongst scientists is simple - we need to find ways to put myelin back on nerves to protect them from damage. We need to remyelinate them. In reality, this task is far from simple, but work has begun and it looks promising.
What do we know?
The MS Society has funded a number of projects looking at myelin repair mechanisms and knowledge in the field is ever evolving. We already know about some key molecules that play a vital role in myelin repair and some of the pathways that are involved. Sophisticated techniques have been employed throughout this search and recently, scientists were able to produce oligodendrocytes in the lab using stem cells.
A novel study that involved screening drugs already available to treat other conditions identified two unlikely candidates as potential myelin repair therapies. One was a drug that is currently used to treat eczema and the other, athlete’s foot! In cream form they wouldn’t be much use but if they could be made into a pill then they could be tested in clinical trials for MS. This would take some time but it is encouraging to discover that everyday treatments like this have the potential to repair myelin.
Clinical trials looking at myelin repair have proved successful too. MD1003, a highly concentrated form of a vitamin that is thought to be involved in myelin production, is currently being tested in a phase 3 trial. The trial involves 144 participants with primary or secondary progressive MS and finishes in 2016. Although the trial is not yet complete, some early results announced at a conference showed that MD1003 has demonstrated some improvement in disability after 12 months of treatment which is encouraging.
Another molecule in the spotlight is anti-LINGO-1 who’s trial is also due for completion in 2016. Anti-LINGO-1 has already demonstrated myelin repair in animal models of MS and more recently it has shown promise in the treatment of optic neuritis. In the current trial, anti-LINGO-1 is being investigated in people with both relapsing remitting and secondary MS to see if nervous system function can be improved over a 72-week timeframe.
So we are full steam ahead and there is no sign of slowing down with some exciting projects on the horizon.
Professor Robin Franklin runs the MS Society funded Cambridge Centre for Myelin repair where a range of myelin repair targets are being explored. Some examples of the work happening in Cambridge include two very interesting projects Dr Mark Kotter is running. The first is an MS Society funded project looking at a protein called FoxO3a which has been found to be harmful in the myelin repair process. Dr Kotter and his group will be looking at what exactly this molecule does during remyelination and how its activity could be altered to help rather than hinder the process.
The second is a collaborative project funded by the MS Society and the Britain Israel Research and Academic Exchange Partnership (BIRAX). The researchers on this project are in search of a molecular hoover. When myelin is damaged by the immune system, it flakes off creating a build-up of debris in the area surrounding the nerve. Cells exist to eat up this myelin debris but if they are not working efficiently, the build-up gets in the way of oligodendrocyte production. Dr Kotter and his group are looking for ways to clean up this myelin waste and subsequently kick start myelin production.
The MS Society is also very pleased to be funding Dr Veronique Miron at the Edinburgh centre for MS Research, through a collaborative Career Development Award with the Medical Research Council (MRC). This prestigious award will allow her to carry out ground-breaking research in the field of myelin repair for the next 5 years.
In her work to date, Dr Miron has shown that a protein called activin-A plays a role in myelin repair. She has already been able to turn on the receptors that activate this molecule to increase oligodendrocyte production. With this funding she hopes to expand on these findings and understand more about how activin-A controls myelin repair. This could pave the way towards new strategies in targeting myelin repair that could be used in clinical trials.
What does all of this mean for MS?
We are in no doubt about the importance of myelin but there are currently no treatments available to repair it. The recent developments in myelin repair research are exciting and provide real potential for future MS therapies. Although this is not something that will happen overnight, it is exciting to see experts in the field uncover more and more about the different molecules and processes involved in myelin repair.
There are a growing number of horses in the myelin repair race and we look forward to seeing them cross the finish line!
Details of each research project:
Targeting activin receptors as a new way to repair myelin (Veronique Miron’s project, who is featured in the DM appeal)
Investigating the role of FoxO3a in myelin repair (Mark Kotter’s project, featured in the DM appeal)
Cambridge Centre for Myelin Repair (although funding does finish in April 2016)
Finding new ways to repair myelin
Discovering new genes involved in myelin repair
Past news stories and blog posts about myelin repair
Breakthrough award for Dr Miron: https://www.mssociety.org.uk/ms-news/2015/09/career-turning-point-dr-miron
Two potential myelin repair treatments identified:
New ‘brain boost’ study gives insight into myelin production:
We’ve also got this video on the youtube channel about the Cambridge Centre:
Hope that helps