MND Australia

Research Directions | September 2023

MND Australia and MND Research Australia research news

Aus & NZ MND Research Symposium
Abstracts have now closed for the upcoming 2nd Australian and New Zealand MND Research Symposium. The two-day event will provide a unique opportunity for MND researchers and those with a lived experience of MND to collaborate, connect and learn. The Research Symposium will have a scientific program running over Friday 17th November and Saturday 18th November with the MND Connect – Research Live session integrating with the scientific program on Saturday. More information, including registration details, are available here.

State of Play
The September edition of State of Play is scheduled for Tuesday 26th September at 7pm (AEST). For this edition we will be joined by Dr Brooke-Mai Whelan and Dr Derik Steyn, from the University of Queensland. Both Dr Steyn and Dr Whelan are 2023 MNDRA Innovator Grant recipients. For this episode we will tackle the subject Eating and speaking in MND - How are researchers targeting appetite and speech decline? Register here.

I had the great experience of attending my first Pan-Asian Consortium for Treatment and Research in ALS (PACTALS) meeting from the 14-16th September in Kuala Lumpur, Malaysia. The meeting was a fantastic opportunity to meet local MND associations from Asia. There was a very strong representation from drug companies at the meeting demonstrating the increasing importance of the Asian region for clinical trials.

Among others, we had the pleasure of hearing from high-profile researchers such as Ammar Al-Chalabi from the UK who developed the 6-step model for developing MND, Merit Cudkowicz from the US who runs the Healey Platform Trial and Jeremy Shefner who is playing a lead role in the global harmonisation of use of the ALSFRS-R scale to increase its utility. A number of up-and coming Australian researchers also presented. 

MND Clinical Research Learning Institute
Do you want to learn how to make an impact in MND research beyond participating in clinical trials and research projects? MND Australia will be hosting the 2nd Australian MND Clinical Research Learning Institute® (CRLI) -- October 13-14, 2023 via Zoom -- and we are now accepting applications to participate in the workshop. Apply here.

Daniel McLoone Major Research Initiative
We recently announced two recipients of the Daniel McLoone Major Research Initiative, which is jointly funded by MND Research Australia (MNDRA) and FightMND. This unique research initiative was made possible by an incredibly generous bequest by Daniel McLoone’s family from his estate following his death. The grants aim to support an outstanding innovative and collaborative project that has the capacity to make a significant impact on Australian MND research. MNDRA worked with FightMND to double the amount available for this grant program enabling us to jointly fund two projects. 

The two projects funded are:

Exploring disease heterogeneity across MND clinical phenotypes using a multimodal, multicentre neuroimaging approach - led by Dr Thanuja Dharmadasa from the University of Melbourne and the Florey Institute of Neuroscience and Mental Health. This long-term study will build an integrative national network to use advanced brain neuroimaging and detailed clinical assessments to follow patients through their disease journey and identify different clinical subgroups.

Australian Preclinical Research ALS (APRALS) Network: a roadmap for effective translation of therapeutics for sporadic MND - led by Professor Bradley Turner at the University of Melbourne and the Florey Institute of Neuroscience and Mental Health. This project will launch Australian Preclinical Research ALS (APRALS), a national collaborative network which aims to accelerate development of novel treatment candidates towards clinical trials in MND. 

Recent clinical trial developments

Clene have provided further updates on the 24-month long-term data cut from the Phase 2 RESCUE-ALS ongoing open-label extension (OLE) study on their drug, CNM-Au8. They report significantly improved survival benefit of 19.3 months and a 52% significant decreased risk of ALS clinical worsening events (defined as the first occurrence of death, tracheostomy, assisted ventilation, or feeding tube placement).

They also announced over 475 years of CNM-Au8 treatment exposure without any identified safety signals across ALS, multiple sclerosis (MS), and Parkinson’s disease participants in CNM-Au8 clinical trials and Expanded Access Protocol programs. Although these reports are very promising, the data has yet to be published and thus has not been subject to peer review. We keenly await seeing the full dataset and publication. 

Brain-Computer Interface (BCI) 
Researchers from UC San Francisco and UC Berkeley created a ground-breaking brain-computer interface (BCI) that allowed a paralysed woman to communicate through a digital avatar. This advancement marks the first-ever synthesis of speech or facial expressions directly from brain signals.

The BCI developed decodes brain signals into synthesized speech and facial expressions, enabling paralysed individuals to communicate more naturally. Instead of recognizing whole words, the system identifies phonemes, the sub-units of speech, enhancing speed and accuracy. The digital avatar’s voice was personalised to mirror the user’s voice pre-injury, and facial animations were driven by software that interpreted the brain’s signals for various facial expressions. 

A study from the ALS Therapy Development Institute in the USA used wearable sensors, worn on four limbs at home during natural behaviour, to quantify motor function and disease progression in 376 individuals with MND. Their approach automatically detects and characterizes sub-movements from passively collected accelerometer data and produces a machine-learned severity score for each limb that is independent of clinical ratings.

They showed that this approach produces scores that progress faster than the ALSFRS-R, meaning lower patient numbers could be used in clinical trials. There is considerable interest in this area worldwide with MNDRA-funded researcher Dr Derik Steyn at the University of Qld also investigating a similar approach although using fewer wearable devices to keep things simpler.

Australian research outcomes

Loss of appetite contributes to weight loss and faster disease progression in MND
This may be due to altered production of hormones that control appetite. A study by Stephanie Howe and colleagues at UQ showed lower levels of ghrelin, a hormone that stimulates appetite and can promote weight gain, was lower in MND patients. Although early results with more work needed, this could suggest this system could be targeted for future treatment.

International research outcomes

Alterations in the levels of blood markers
It is thought that changes in metabolism may precede the onset of motor symptoms in MND. A group at the University of Oxford aimed to seek evidence for alterations in the levels of blood markers collected routinely in the primary care setting prior to the onset of motor symptoms in amyotrophic lateral sclerosis.

They showed changed levels of cholesterol markers preceded symptom onset. This further supports a role for the cholesterol system in MND which may inform our understanding of the disease process as well as identify possible biomarkers.

Other research 

Research investment
In a league table of how countries are currently investing in R&D as a percentage of GDP, Australia was 24th of 29 OECD countries committing 1.68% of GDP (the average was 2.71% with the US committing 3.46% and the UK 2.93%). The figures continue a 14-year downward trend in national R&D investment for Australia.

If we keep going the way we are, in five years we'll be among the lowest of all OECD countries. This really demonstrates the amazing quality of Australian MND researchers in an underfunded system and highlights the value of organisations such as MND Research Australia supporting research beyond government programs.

Readable Research
A group of scientists from the Sheffield Institute for Translational Neuroscience at the University of Sheffield and the National Institute for Health and Care Research (NIHR) Sheffield Biomedical Research Centre (BRC) in the UK have developed the website producing clear simple summaries of scientific papers in the motor neurone disease, Parkinson’s disease, dementia and stroke research fields. The team has people with lived experience providing feedback on the summaries before they are published to make them as ‘readable’ as possible.