More than 130 passionate researchers gathered at the Queensland Brain Institute in sunny Brisbane on Friday 21 October to attend the MND Australia Research Meeting 2016. This year’s meeting included 21 excellent oral presentations and 35 stimulating poster presentations throughout the day. A fantastic community research event ‘MND Connect’ was held the next day to bring together researchers, clinicians and community in an interactive forum. Together the two days showcased our vibrant motor neurone disease (MND) research community in Australia and the breadth of current research projects.
Executive Director of the Queensland Brain Institute Professor Pankaj Sah opened the meeting. MND Australia President David Ali followed with news of grants that had been awarded at the previous day’s Grants Allocation Meeting: $3.75 million of funding was allocated for MND research to start in 2017. This includes two post-doctoral fellowships, 29 grants-in-aid, and a new award for 2017, the Betty Laidlaw MND Prize, which aims to support an outstanding mid-career researcher. Australian philanthropist John Laidlaw presented the Betty Laidlaw Prize to Dr Catherine Blizzard from the Menzies Research Institute, University of Tasmania, for her project ‘TDP-43 misprocessing drives synaptic deficits and ALS’. A special award was also presented to Professor Dominic Rowe AM in recognition of a decade of exceptional leadership of the MNDRIA Research Committee between 2003 and 2013. On accepting his award, Professor Rowe reflected on the progress of MND research over the last few years and how, with a growing network of clinicians and scientists dedicated to decoding the disease, things have changed for the better.
Twenty-one speakers reported on the outcomes of their research projects supported by the MND Research Institute of Australia in 2016. Topics ranged from the microscopic, aiming to better understand MND at the cellular level, to the clinical aspects of MND including metabolism (energy needs and expenditure), exercise, and the tendency for motor neurons to be trigger happy (hyperexcitable) in the motor cortex of the brain.
The theme of the first session was new models in research to understand the causes of MND. We heard about studies in fruit flies, zebra fish and mice from A/Prof Greg Neely (USyd), Dr Nicholas Cole (MQU), and Dr Adam Walker (MQU) respectively. Each model organism has its own advantages and together they provide an array of techniques for researchers to test new therapeutic strategies. Importantly, the first session also included talks from researchers looking at MND from a different perspective. We heard about the effects of cellular stress in motor neurones and the possible involvement of structures called “paraspeckles” from Western Australian researcher Dr Archa Fox (UWA) while A/Prof Julie Atkin (MQU) shared her work on the potential role of DNA damage in MND.
The accumulation and deposition of pathological proteins is a common hallmark of MND and was a common theme of the next session. Protein homeostasis refers to maintaining the level of proteins inside cells at a steady state. When this system is disrupted and protein production runs unchecked, large protein aggregates form, which become toxic to cells. It is a process that has gone awry in MND, as in other neurodegenerative diseases like Parkinson’s and Alzheimer’s, and if detectable, may serve as an early warning sign. Dr Danny Hatters (UMelb) is developing a tool to measure protein homeostasis in cells grown in culture in the lab. Similarly Dr Shu Yang (MQU) is aiming to do the same thing using skin cells donated by MND patients and by focusing on one aspect of protein homeostasis – protein removal (or degradation). Cellular systems of protein removal are likely to be dysfunctional in MND; Dr Darren Saunders (UNSW) and Dr Albert Lee (MQU) both provided evidence that this is the case. It is thought that once proteins accumulate in neurons these aggregates might be able to travel from one cell to another in the brain – although this had never been observed. Promisingly, Dr Marco Morsch (MQU) provided striking evidence that this can occur in a living zebra fish brain.
In the afternoon session, research focusing on potential therapeutic treatments under study and drug delivery approaches was discussed. Dr Peter Crouch (UMelb) updated the audience on his research on the effect of copper malfunction in MND. Metal ions like copper are essential for the activity of proteins and enzymes in our cells; without copper, an enzyme called ceruloplasmin cannot do its job in the central nervous system (CNS). As of this year, Dr Crouch’s research has moved to a preliminary clinical trial to test a potential therapeutic named copper-ATSM, which aims to correct this mineral malfunction in MND. Meanwhile, A/Prof Peter Noakes (UQ) has been studying another drug, PMX205, in a mouse model of MND. This drug has shown a therapeutic effect in mice when administered before or shortly after the onset of symptoms. On a different tact, Dr Sandy Shultz (UMelb) is investigating the link between traumatic brain injuries and MND in rodent models, which may provide alternative pathways for drug development. To improve the delivery of therapeutics to motor neurones, a common hurdle in drug development for MND, Dr Mary-Louise Rogers (Flinders University) and Dr Bradley Turner (UMelb) are developing “immunogenes” while Dr Justin Yerbury (UoW) presented a liposome-based approach. Both strategies use specific antibodies chosen for their ability to direct the delivery of a gene therapy or drug from circulation to motor neurones, the site of the disease.
The final session wrapped up the day of talks at the clinical end of the research spectrum. Cortical hyperexcitability (those overactive neurones in the cortex of the brain) is believed to be an early feature of the disease. This is being studied at the cellular level but can also be observed in patients diagnosed with familial or sporadic MND. Motor neurones are vulnerable to damage from hyperexcitability; A/Prof Tracey Dickson (UTas) and Dr Catherine Blizzard (UTas) are studying why. It may be because the usual mechanisms to inhibit neuronal overactivity are dysfunctional in MND or that protein aggregates of TDP-43, the major MND-associated protein, disturb neurone-to-neurone communication. In line with A/Prof Dickson’s finding, Dr Nimeshan Geevasinga (USyd) reported that in people with C9ORF72-familial MND and those with sporadic MND the normal inhibitory neuronal activity of the motor cortex is reduced. This work tells us that these two different cohorts of patients share a common physiological abnormality that causes cortical hyperexcitability.
As for more immediate help for those currently affected by MND, Dr Michael Lee (UTS) told us that patients can maintain what they’re currently doing for exercise, but not to exercise to fatigue. Instead, intermittent exercise below the level of maximum exertion can be beneficial as it helps to restore neurone activity to normal levels. In terms of energy requirements, Dr Derik Steyn (UQ) emphasised that no two MND patients are the same and their energy needs vary greatly, but hypermetabolism and weight loss are universally detrimental to disease progression. A patient’s intake of energy from their diet alters the course of disease: energy supplementation slows disease progression while energy restriction accelerates it. So a calorie-rich diet as well as whatever low-moderate amounts of exercise one is capable of are two ways a person with MND can actively help themselves out and improve their quality of life.
The evening poster session was held together with a drinks reception to close the research meeting. The Poster Committee reviewed twelve student posters and the prize for best poster was awarded to PhD student Andi Lee from The University of Queensland for her poster ‘Mutation of TDP43 leads to disrupted transmission and morphology at neuromuscular junctions’. It was great to see the next generation of researchers in the field present their outstanding work.
The following day, people living with MND and their families were invited to attend the ‘MND Connect’ community event. Ms Carol Birks, CEO of MND Australia, began with an informative talk about the economic cost of MND care and research in Australia based on the recent report by MND Australia and Deloitte Access Econ. Across the day, patients and their families were given a snapshot of the progress in research and clinical care. The focus was on new clinical trials open in Australia (for Cu(II)ATSM and Triumeq) and clinical registries, like the Australian MND Registry. This research was presented alongside stories of patient experience and panel discussions. The consensus of the day was that many valuable conversations were had between patients, their families, clinicians and scientists which would certainly direct future research questions.
Clare Watson, Isabella Lambert-Smith, Justin Yerbury and Stephanie Williams