MND Australia

Research Directions | October 2023

MND Australia and MND Research Australia research news

Applications for MND Research Australia 2024 grants are currently in the review process, with our Grant Allocation Meeting scheduled to take place on the 10 November 2023. We will be able to announce successful outcomes soon after this meeting.

We received close to 100 abstract submissions for the the Australia and New Zealand MND Research Symposium, which will be held in Wollongong on the 17–18 November 2023. A final program will be released soon, and registration is now open to attend the symposium either in person or online.

Recent clinical trial developments

The MND-SMART trial in the UK is a platform trial that tests multiple drugs in Phase 2/3 trials in parallel. This approach reduces resource requirements and enables all of the drugs to be tested against a single placebo group, meaning participants have a higher chance of receiving active treatment.

The first two drugs to be tested within this platform were memantine and trazodone. The trial was designed so that data could be checked regularly to see if any drugs were working or not. This approach allows researchers to either keep testing, or to stop the trial early if there is no benefit.

Independent committees have looked at the data at an interim analysis and decided that there is no benefit from memantine and trazodone and have concluded that there is enough evidence to stop testing them. Although drug trial fails are always disappointing, it is good to have a definitive answer early and enable the resources to be applied to new potential treatments. 

Testing of a third drug called amantadine commenced in April 2023 and several new drugs will be introduced to the trial in 2024 and 2025.

The MND-SMART trial has also undertaken a study to investigate factors affecting recruitment and retention of trial participants. They found that people with MND are highly motivated to engage in research, but older individuals remain significantly less likely to participate. We therefore need to focus on initiatives that support older people to participate in trials.

The phase III clinical trial of TUDCA-ALS, which examined the safety and efficacy of tauroursodeoxycholic acid (TUDCA) in ALS has completed. Data analysis will commence soon, with top line results expected to be announced by the end of December 2023.

TUDCA is one of the two components of Amylyx’s drug Relyvrio, which was recently approved in the US and Canada. It will be very interesting to compare the results of TUDCA alone with the Relyvrio combination therapy when all the data is available. 

The European Medicines Agency (EMA) has completed a re-examination of Relyviro and confirmed its initial negative opinion on the Marketing Authorisation Application for Relyvrio for the treatment of ALS in the European Union. The Agency has concerns that the main study did not show convincingly that Relyvrio was effective in slowing down the worsening of the disease or increasing survival.

US National Institutes of Health (NIH)  grant program
In 2021 the US government passed the Accelerating Access to Critical Therapies for ALS Act (ACT for ALS). Part of this program required the US National Institutes of Health (NIH) to establish a grant program for research using data from expanded access to investigational drugs for individuals not otherwise eligible for ALS-related clinical trials. This month the NIH has made three awards for this grant program:

  1. An Intermediate-Size Expanded Access Protocol for ALS with Pridopidine
  2. Intermediate-size Expanded Access Protocol for CNM-Au8 in ALS
  3. Intermediate-Size Expanded Access Trial of Autologous Hybrid TREG/Th2 Cell Therapy (RAPA-501) of ALS

Australian research outcomes

Longitudinal changes in intrinsic motoneuron excitability in amyotrophic lateral sclerosis are dependent on disease progression.
Led by Gabriel Trajano at the Queensland University of Technology (QUT) and Rob Henderson at the Royal Brisbane & Women's Hospital, the study directly measured the activity of motoneurons in people with MND. They compared activity in weaker and stronger muscles and tracked this over time to see how it changed with disease progression. They saw key changes as muscles became weaker, suggesting that using these measurements to follow disease will need to take into account a number of factors.

RNA sequencing of peripheral blood in amyotrophic lateral sclerosis reveals distinct molecular subtypes: considerations for biomarker discovery.
Led by Natalie Grima and Kelly Williams at Macquarie University, this study looked at whether RNA sequencing could provide potential biomarkers for MND. RNA sequencing measures the levels of all gene activity in a sample and it is thought that cell activity changes as MND progresses, and this could be captured through looking at cell activity in blood samples. They showed that blood RNA sequencing can identify diagnostic biomarkers and distinguish molecular subtypes of MND.