As well as all the networking, debate and new information being shared, the International Symposium on ALS/MND is also a time to celebrate achievements by the giving of awards. The Biomedical and Clinical poster prizes are an opportunity to recognise and celebrate the excellent research and clinical practice being conducted by those early in their career.
Now in its fourth year we hope that the poster prizes will help give the winners career a boost, and give them the encouragement and motivation to continue in MND/ALS research. This year the Panel selected an international group of winners: Dr Albert Lee from Australia and Elsa Tremblay from Canada were jointly awarded the Biomedical poster prize and Ruben van Eijk from The Netherlands won the Clinical poster prize. Each winner received a certificate and a glass engraved paperweight.
The prize winning research ranged from understanding the consequences of a newly discovered gene mutation linked to MND, to why the junction between nerves and muscles is one of the earliest signs of motor neurone damage, to a new statistical analysis to make clinical trials quicker and more efficient. Below I’ve explained more about the research that the winners presented.
Understanding of why CCNF mutations cause MND
Dr Albert Lee is a post-doc researcher based at Macquarie University in New South Wales, Australia. In April 2016 colleagues at Macquarie found a link between mutations in a gene called ‘CCNF’ and MND and FTD. Hot on the heels of making this link, Albert is investigating how mutations in CCNF cause motor neurones to die in MND.
CCNF and the protein it makes, called Cyclin F is involved in labelling proteins ready for recycling within the cell. Albert found that the mutated Cyclin F added more labels than normal, as the labelling function couldn’t be switched off. The effect of this was that some proteins were recycled before they needed to, which in turn led to lower levels in the cell to carry out their normal function. He found that these prematurely recycled proteins controlled cell survival. Thus lower levels of these proteins may be one of the reasons for motor neurones dying in MND. More work is need to confirm these finding for definite.
How is the junction between nerves and muscles damaged early in MND?
We have different types of muscle that allow us to do different things – for example, it’s a different type of muscle that allows people to run marathons (slow muscle) in comparison to the type of muscle that helps people to sprint (fast muscle). Where motor neurones and muscles meet is known as the neuromuscular junction. There is evidence that in MND the neuromuscular junction is one of the first parts of the motor neurone to get damaged.
Elsa Tremblay’s PhD research at the University of Montreal in Canada is looking at the way motor neurones connect to and stimulate muscles, and how this changes in MND. In particular, she’s looking at how different types of muscle are affected in MND.
Elsa examined the electrical activity of the fast and slow muscle types at different stages of MND disease progression. As she was looking at a mouse model of MND, she could see what happens to the fine balance of electrical signals before any signs of MND were seen. She found that electrical signaling at the neuromuscular junction is different in mice with MND, compared to healthy mice. Differences were found depending on the type of muscle and also depending on the stage of the disease. All this information is important to help us target drugs to slow down or stop the damage seen at the neuromuscular junction in MND.
New ways of designing clinical trials
The clinical poster prize was won by Ruben van Eijk from Utrecht in The Netherlands for his research looking at clinical trial design. A traditional way of running a clinical trial is to decide before you start how many people you need to take part and for how long, so that you can tell for sure that a drug does or doesn’t work. Researchers have to wait until the end of the trial before the analysis on whether it has worked can be carried out. This statistical analysis is important, as it is part of the evidence that regulators such as the MHRA in the UK or the FDA in USA ask for when considering whether to licence a drug.
There are now new statistical methods available that allow researchers to continually analyse the results of a clinical trial as they go along. The advantage of this is that they may get an answer quicker than a traditionally-designed trial. However, before a new trial uses this new method of analysis, it is important to find out if it works. Ruben van Eijk used the data from an old clinical trial in MND that didn’t find a beneficial effect and re-analysed the data using the new methods. He still found that the drug didn’t work. However, with the new method he found you would need slightly more people to take part in this trial, but that the trial could’ve been shorter and involved fewer visits to the hospital.
It was important to highlight his findings, so that those designing trials in the future have greater confidence that new types of analysis do work and can lead us to get answers quicker on whether the drug works in MND or not.
You can read more about clinical trials and how they are designed in our clinical trials information sheet.