Preparing for the windy city: Symposium update

Every year we are responsible, as an Association, for organising the BIGGEST international conference event of the year on MND. The 23rd International Symposium on ALS/MND will return, after 16 years, to the windy city of Chicago from the 5-7 December this year.

This event is one of the most exciting events in the research calendar for those involved in MND research, and it promises to be full to the brim with exciting, cutting edge presentations. Scientists, clinicians and health care professionals across the globe come together every year for this stimulating event.

The deadline for abstract submission was back in May and we’ve been incredibly busy since then in compiling the abstracts for this year’s Symposium.

This year we received 419 high quality abstracts from across the globe, totalling 172,581 words! The Symposium Programme Committee, chaired by Prof. Wim Robberecht, had to review every single one of these in order to compile a stimulating and varied programme.

This year the Symposium will consist of a total of 96 oral presentations, with joint opening and closing plenary sessions on risk factors of the disease and the challenges of translating knowledge to treatment. There will be parallel scientific and clinical sessions exploring a wide variety of topics from target pathways, disease models and biomarkers, through to cognitive changes, multidisciplinary management and clinical trials. The final programme offers plenty of new ideas and key insights, particularly into the newly discovered C9ORF72 gene.

The Symposium will also see 251 poster presentations, and 55 work in progress poster presentations, showcased on a wide range of scientific and clinical themes that all sound incredibly interesting!

Me and Kelly have spent the past several weeks editing, formatting, proof reading and compiling all of these abstracts, which were sent to the publisher last week. The final document was 290 pages long and consisted of 150,096 words! The next stages of this process for us are to receive the proofs back from the publisher so that we can double, and triple, check them before they are ready for the Symposium. We will also be letting authors know their final poster numbers and timings so that they can get their presentations in order for the big event.

The full Program is available NOW on our website to give you an insight into the themes, and topics, that will be presented this year

Mediating the delicate balance between protection and damage

The Opening Session theme on how the disease progresses within the Central Nervous System (CNS) continued with the presentation by Prof Stan Appel from Baylor College of Medicine, Huston on neuroinflammation.

Examination of post-mortem brain and spinal cords from people with MND shows clear evidence of inflammation (although Prof Appel was quick to point out that this is not the same as occurs in ‘primary’ inflammatory conditions such as multiple sclerosis). Similar patterns are seen in human MND spinal cord and in SOD1 mice, suggesting that at least for this aspect of the disease, SOD1 mice may be a good model of human MND.

He went on to explain how migroglia, the ‘innate’ immune cells of the CNS, help mediate a delicate balance between protection and damage. The speed of progression in MND appears to be dictated by this balance.

Prof Appel showed that SOD1 mice exhibit two phases of disease: an early slow phase, where the microglia release a series of protective factors, and a rapid secondary progressive phase where levels of these protective markers fall and are replaced by a rise in ‘pro-inflammatory’ toxic factors. Of course, strains of lab mice are so inbred that they are genetically very similar and develop the disease in a uniform manner. Humans on the other hand are very different, as is the way the disease progresses between one individual and the next, so the two stages of disease are not easy to demonstrate in MND patients. However, by examining the inflammatory factors present in patients with very rapid progression against those with slower progression, he was able to show that the factors associated with the second ‘rapid progression’ phase in mice were also present in the rapidly progressing patients. He suggested that this may assist clinicians in predicting how the disease is likely to progress in patients at an early stage in the disease.

It is relatively easy in cell culture studies to tilt this balance from protective to toxic, but could the balance be tilted the other way in patients, as a therapeutic strategy? Certainly, in response to a question from the floor, he suggested that greater attempts should be made in this direction, commenting, “The whole issue of immunosuppressant drugs in MND needs to be re-opened. But – you can’t just take down all immune responses in an uncontrolled way. You need drugs that are much more selective”.

Read our official day one symposium press release on our website.

Copying, transporting and creating proteins – what could possibly go wrong?

Proteins are the building blocks of our cells and have a variety of important roles within our bodies. The instructions for how to build our proteins sit within our DNA, our genetic code in the control centre of our cells (the nucleus). There are many steps to go through from reading that ‘raw’ instruction to ending up with a fully functioning protein.
However, the amount of information held within our genetic code is so huge that only small segments of it are read and transferred to the factory floor, as and when they are needed. These copies, known as messenger RNA, are small enough to be transported to the ‘factory floor’ of the cell to large machine-like entities called ribosomes where the copy is read, and used to create the resulting protein.
When I was doing my A levels and later at University (yes, that long ago!), we were taught that only 1% of the genetic code ever made it to the factory floor. This held true until a couple of years ago. However, as explained by Professor Bob Brown in his presentation at the ‘RNA and protein processing’ session this afternoon, such is the change in our knowledge in that area, we now know that 95% of our genetic code makes it through to the first step of making proteins.
This was a key piece of context in trying to understand the role that TDP43 plays in functioning cells – never mind specifically in motor neurones or in cases of the presence of damaged TDP43 in MND!
Professor Brown, University of Massachusetts Medical School, Boston, USA went on to give an enlightening review of what has been uncovered about this fascinating protein (TDP43) so far. Once the protein of TDP43 has been correctly made, its function is to go back and ensure that other proteins are correctly made too – the so called ‘reading helpers’ of the cells, or ‘editors of instructions’. Another new fact to me from this talk was that TDP43 is involved in editing or reading up to ONE THIRD of all proteins within the cell. That’s a city fat cat type of job! So how is it all related to it’s function in MND?
Some elegant experiments have shown that TDP43 regulates how many copies of it’s own protein are made. However, the regulation takes place in the control centre of the cell (see the top of this blog). If TDP43 gets stuck or waylaid on the factory floor, it can’t get back to press the stop button in time. So it’s thought that more and more protein is made, accumulating on the factory floor until that accumulation can be seen as the protein deposits so characteristic of what you see of motor neurones affected by MND down the microscope.
Part of the editing work that TDP43 does so well is known as ‘splicing’. In true ‘Blue Peter’ style, here is a description of that process that Kelly prepared before I flew out to Sydney:

Alternative protein
One gene can hold the instructions for a number of different versions or variants of a protein. These variants are created when different parts of the gene are used in alternative combinations. This is a normal process and it’s called ‘alternative splicing’. This complicates matters in terms of genetic research, as even though we have approximately 20,000 genes, we could potentially have a much higher number of functional proteins because of alternative spliced variants.

How does alternative splicing work?
The picture (below) depicts a simple version of how a gene can be alternatively spliced, given three ‘parts’. The example demonstrates that the first version of the protein is made up of parts 1, 2 and 3, whereas version two is made up of only parts 1 and 3. These resulting proteins would go on to function in our bodies in potentially different ways. It is therefore possible for a number of different proteins to be created given one set of original instructions in the genetic code.



Read our official day one symposium press release on our website.

The calm before the storm

MND researchers from around the world who are hoping to present their work at this year’s International Symposium on ALS/MND are (we hope!) preparing to submit to us brief summaries of their proposed presentations.

These summaries, known as abstracts, have been trickling in since March. Based on the form of earlier years, the trickle will become a tsunami in the last 48 hours before the 3 May deadline – the numbers are likely to leap up from the twenties into the several hundreds. Researchers like to cut it fine!

Meanwhile, the research development team waits with bated breath. It’s hard to organise a stimulating symposium programme from just 26 abstracts but we have faith that the international research community will come up trumps!