Disease mechanisms: Highlights from Glasgow

This blog is part of the ‘Highlights from Glasgow’ collection of articles, where you can read about the content of some of the talks and posters presented at the 29th International Symposium on ALS/MND.

Several sessions at the Symposium focused on how impairments in key neuronal structures in MND contribute to the development and progression of the disease, and how these could be targeted with therapeutics.

Prof Spires-Jones (C16) opened session 4A with a discussion of the role of synapses in neurodegeneration. Synapse dysfunction and loss is seen in many neurological diseases, including MND, Alzheimer’s disease and Dementia with Lewy bodies. The commonality of synapse loss across these diseases makes it a key therapeutic target, and in addition, most neurological drugs work at the level of synapses, making them a very ‘druggable’ target. Prof Spires-Jones summarised data from her team and others that showed that in MND, synapse degeneration in the frontal cortex is associated with cognitive decline, and damaging TDP-43 protein is found in synapses. Targeting these pathways could be beneficial to prevent or treat MND.

We also heard an interesting talk from Prof Schiavo in session 5A (C29) on the use of axonal transport as a therapeutic target. Deficits in axonal transport are found in many neurological diseases, including MND.  These deficits appear before/at disease onset and are likely to be important in the development of MND. Schiavo talked us through data that showed that the p38 MAPK signalling cascade, which is important for axonal transport, is increased in the SOD1 mouse model of MND, and that long-term treatment with a p38 MAPK inhibitor partially restores physiological function in MND neurones in vitro and in vivo. Another example showed that inhibition of the insulin-like growth factor-1 receptor (IGF1R) (which is overexpressed in MND patients) restores axonal retrograde transport in a SOD1 mouse in vivo, providing further evidence of the possible beneficial effects of targeting key pathways linked to axonal transport. The take-home message was that axonal impairments are reversible and can be modulated by small molecule inhibitors.


Find out more about the topics discussed in Glasgow on our Periodic table of Symposium at www.mndassociation.org/symplive.

Tissue biomarkers: Highlights from Glasgow

This blog is part of the ‘Highlights from Glasgow’ collection of articles, where you can read about the content of some of the talks and posters presented at the 29th International Symposium on ALS/MND.

Around the globe, teams are working to find tissue biomarkers for MND and there some promising candidates coming through, some of which were explored at session 8C of the Symposium: Tissue Biomarkers.

We first heard from Rebekah Ahmed (C83), who presented her data on possible neuroendocrine and metabolic biomarkers. Ahmed and her team analysed several proteins related to these systems in the blood of 127 people with either MND or MND with FTD and compared them to controls. The Neuropeptide Y protein (NPY), which is related to eating habits and food intake, was found to be higher in people with MND and MND-FTD, and lower in people with FTD, shining the light on a possible biomarker. All patients also had an increase in leptin and insulin levels, highlighting the need to examine how these neuroendocrine changes affect underlying disease pathology.Read More »

How is tissue donation helping us to solve the MND puzzle?

Each year, the MND Association dedicates the month of June to raising MND awareness. This year, we focus on the eyes – in most people with MND the only part of their body they can still move and the only way left for them to communicate. Alongside the Association-wide campaign, the Research Development team selected six most-enquired about topics, which we will address through six dedicated blogs.

Last year, I wrote about our trip to a brain bank. Here, we learned about how people can arrange to donate their tissue (brain and spinal cord) to tissue banks after they die, and how it is stored and used in MND research all around the UK.

What you might be asking is: what can tissue actually tell us about MND, and how will this help us find new treatments?

To find new drugs that can beat this disease we first need to understand what is going on in the brain, which is very difficult to study in living people. This is why post-mortem tissue from people with MND is an invaluable resource. Below are four reasons why tissue donation is so important.Read More »

Our Visit to a Brain Bank

Brain banks are a vital resource in MND research. The MRC London Neurodegenerative Diseases Brain Bank was established in 1989. It is part of King’s College London and King’s College Hospital, and is part-funded by the Medical Research Council (MRC).

The new brain bank building at King's
The new brain bank building at King’s

After 18 months of planning, the bank has recently relocated into a bright terracotta building, fit with state-of-the-art equipment and plenty of space to teach in.

To celebrate the move, my research team colleague Martina and I attended their open day. We heard some interesting talks then got to meet the team, tour the labs, and even see a brain dissection! Here’s what we found out…Read More »

Using stem cell technology to understand more about how MND and FTD develop

The MND Association are funding Prof Kevin Talbot, Dr Ruxandra Dafinca (née Mutihac) and colleagues at the University of Oxford, who are investigating the link between the C9orf72 and TDP-43 genes in MND. We wrote about this research earlier in the year. As we’ve recently received their first year progress report we wanted to give you an update on what they’ve achieved.Read More »