In early December, the 27th International Symposium on MND was held at the Dublin Convention Centre, located on the banks of the river Liffey. The conference ran over 3 days and was attended by over 800 delegates made up of MND researcher’s, neurologists, carers and MND patients from all over the world. It was an exciting time to come together and share many exciting updates in the MND field. After an enormous welcome (céad míle fáilte – one hundred thousand welcomes) from the Irish MND association the symposium began! Here are some highlights from the presentations.
Dublin Convention Centre
The first speaker was Dr Roel Vermeulen from Utrech University, Netherlands, who spoke about his work on investigating environmental risks associated with MND. In describing how both our genes and environment can contribute to MND, he quoted Dr Oz saying “it’s your genes that load the gun, but it’s the environment that pulls the trigger”. The next speaker was the incredibly quirky Dr Rick Bedlack from Duke University, USA. He spoke about a controversial topic, but something that all MND patients and their families would be familiar with – Alternative off-label therapies (AOTs). These are therapies that have no scientific evidence of efficacy but are often described as “cures” and are combined with anecdotal evidence such as patient videos. He stated that 50% of all MND patients will try some form of AOT and while most AOTs are generally regarded as safe there is the potential risk of physical harm to the patient and therapies are often very costly with no benefit. Dr Bedlack created the website ALS Untangled which analyses, scores and reports their findings on what is known about current AOTs. He also presented some information about his investigations into the incredibly rare cases of MND reversal. Reasons why these few patients have improvements or reversal of symptoms are difficult to identify but may be due to the patient having a very different type of MND (or not really having MND at all), having some resistant or protective factors in their genes or proteins or due to something that the patient may be doing or taking that is treating their MND. Dr Bedlack is now focusing part of his research on studying these patients, to determine what it is about these patients that makes them resistant to MND progression in a hope of finding some clues to help other MND patients.
The next two sessions were focused on RNA (our single-stranded DNA from our previous Blog) and described some new advances in technology including using artificial intelligence (IBM-Watson) to discover new genes and proteins involved in MND. The final session of the first day was on the topic of our most recent blog, protein misfolding and aggregation. This session had 6 speakers, 3 of which were Australians! The highlight from this session were the videos from Dr Morsch’s zebrafish model of MND showing live imaging of the inflammatory cells, microglia, engulfing damaged motor neurons and clearing away protein aggregates.
Image of a zebra fish and one where it’s motor neurons have been labelled in green. On the right is a close up of the green motor neurons and a microglia (labelled in red) surrounding the motor neuron (adapted from Morsch et al., 2015).
Day 2 began with some presentations on therapeutic strategies and focused on the use of human patient stem cells as MND models. After morning tea Associate Professor Özdinler presented some beautiful pictures of the upper motor neurons in the brain (also called Betz cells). Her research showed that even during the early stages of disease bubble-like structures called vacuoles accumulate along the motor neuron’s branches and high powered images showed these vacuoles were being used to break down the contents of the degenerating motor neuron. This presentation was followed by 4 more talks (including 3 Australian speakers) presenting on copper proteins, DNA damage and oxidative stress.
Prof Ozdinler presenting her work in MND patients and images of upper motor neurons in the brains of healthy and MND mice. Large bubble-like vacuoles can be seen in the MND motor neurons (adapted from Geevasinga et al., 2016).
Next there was a session on symptomatic treatments where talks on the effect of Cannabis Satvia extract, aerobic exercise and meditation training on MND patients were reported. The alternative session was on mouse models of MND and included a presentation from a group in Japan that showed positive effects of the drug Perampanel in their MND mouse model.
The last session of the day was on evolving biomarkers. A biomarker is a naturally occurring gene or characteristic that can be measured in a person and changes with disease. In MND a few biomarkers (p75 and neurofilament heavy chain) have been identified but further validated markers are needed. This session presented a number of MRI imaging tools that can be used as readouts of an MND patient’s disease progression which will likely help with determining the outcomes of future clinical trials.
On the last morning of the conference there two great sessions were running. The first was on the interactions between neurons and glia – the support cells that also play a role in MND progression. The other session was an update on current MND clinical trials. Results from 5 trials were reported. The drugs included Edavarone, Ibudilast, Rasagiline, Tirasemtiv and the SOD1-specific drug Pyrimethamine. The outcomes from these trials will be summarised in our next Cure for MND Research Blog.
The neuroinflammation session began with a great introduction from Prof Lynch from Trinity College in Dublin. She spoke about the breakdown of the blood brain barrier (from Blog 1) with ageing and in disease and described how this allows immune cells from the periphery into our brains and spinal cord. Dr Stan Appel shared some preliminary data from his clinic where they had performed bone marrow transplants on 3 patients to increase the numbers of protective immune cells called Tregs. Two talks on microglia showed that keeping immune cells in their resting state rather than their activated state were beneficial in mouse models of MND. In particular, Dr Barbeito showed that administration of his drug, Masitinib, which acts on immune cells in the brain and spinal cord, extended survival when administered in the very late stages of disease.
The final closing session reported on the Airlie House Clinical Trials Guideline Workshop which aims to standardize the way that Clinical Trials are designed, run and reported. This will improve the outcome for patients and reduce false-positive trial outcomes. There was also late breaking news with updates on two clinical trials, one using intraspinal and intramuscular injections of bone marrow-derived stem cells and the other using arimoclomol to reduce SOD1 protein aggregates. Lastly, the MND alliance presented an invitation to next year’s symposium in Boston, USA where an update on all the findings from the next year’s MND research will take place!
Stay tuned for the next blog coming soon which will summarise the findings of the MND clinical trial presented in Dublin!