Research Directions | March 2023

MND Australia and MND Research Australia research news

• MNDRA, in conjunction with GenieUs ran the first Australian MND Clinical Research Learning Institute (CRLI) in November 2022. Another is being planned for mid-2023.
• The MNDRA State of Play webinar series will be restarting in March 2023. If you missed previous episodes, recordings are available here.

Recent clinical trial developments

AMX0035/Albrioza/Relyvrio

• Following approval in Canada in June 2022, the US Food and Drug Administration (FDA) announced in September that it has approved the therapy RELYVRIO™ (sodium phenylbutyrate and taurursodiol), developed by Amylyx, for the treatment of adults with amyotrophic lateral sclerosis (ALS). RELYVRIO (previously known as AMX0035) significantly slowed the loss of physical function in people living with ALS in clinical trials.
• We have had preliminary discussions with Amylyx around them applying for approval in Australia. Unfortunately, they are a small company and are currently prioritising increasing production and focussing on the North American and European markets.

Tofersen

• The pharmaceutical company Biogen have developed a treatment specifically for those carrying SOD1 mutations. The FDA is currently considering Tofersen for approval and will announce their decision in April 2023.

CNM-Au8

• Clene, a small pharmaceutical company, reported results for a Phase 2 trial for their treatment, CNM-Au8.
• Disease measurements, ALSFRS-R (Revised Amyotrophic Lateral Sclerosis Functional Rating Scale) and Combined Assessment of Function and Survival (CAFS) and slow vital capacity (SVC), did not show a statistically significant change over the 6-month trial.
• There did appear to be an increase in survival however which was consistent with a previous trial run in Australia.
• Clene have also reported data from an open-label extension (OLE) of this and the Australian trial and the data appear to show greater benefit with longer treatment with the drug.

 Masitinib

• A Pharmaceutical company, AB Science, has applied to the European Medicines Agency (EMA) (EU equivalent of TGA) for masitinib (Alsitek) in the treatment of ALS.
• Masitinib is a tyrosine kinase inhibitor and is thought to decrease neuroinflammation and exert neuroprotective effects.
• The application is based on results from the phase 2/3 AB10015 study and its long-term survival follow-up which showed a significant decrease in ALSFRS-R. This corresponds to a 27% slowing in the rate of functional decline. There was also a 44% reduced risk of death.

CuATSM (Copper ATSM)

• We are still awaiting to hear the outcomes of the Australian-run CuATSM trial. This trial was completed more than 12-months ago and it is very disappointing that the company running the trial, Collaborative Medicinal Development Pty Limited, has yet to report on the outcome. 

RNS60

• RNS60 is proposed to have anti-inflammatory properties. The results from a 6-month phase 2 trial were reported at the recent International Symposium hosted by the UK MND Association.
• There were no statistically significant differences between the treatment and the placebo on any of the biomarker measures or when measuring function using the ALSFRS-R. There were hints of promising trends when looking at Forced Vital Capacity (FVC), which is a measure of respiratory function. The results from this trial support the need for additional trials to investigate the use of RNS60 in people living with ALS/MND further.

Australian research outcomes

Lower Hypothalamic Volume with Lower BMI is Associated with Shorter Survival in Patients with ALS published by Shyuan Ngo’s and Derick Steyn’s groups at the University of Queensland (UQ)

• It is important to understand the relationship between weight loss and faster disease progression in MND. This study showed that patients with a dysfunctional hypothalamus, part of the brain critical for regulating energy intake and metabolism, that had weight loss, were also at a greater risk for faster disease progression and earlier death. Early identification of these patients will help guide disease management.
• This work has been partially funded by MNDRA

Altered SOD1 maturation and post-translational modification in amyotrophic lateral sclerosis spinal cord published by Kay Double’s group at the University of Sydney

• Mutations in the SOD1 protein are known to lead to MND due to the protein behaving abnormally in neurons. This study demonstrated that even in patients that do not have the SOD1 mutation, the SOD1 protein still behaved abnormally and could contribute to disease. This means that potentially, SOD1 targeting therapies could work for patients not carrying SOD1 mutations.

Assessment of Safety of a Fully Implanted Endovascular Brain-Computer Interface for Severe Paralysis in 4 Patients - The Stentrode With Thought-Controlled Digital Switch (SWITCH) Study 

• This research was led by Thomas Oxley who is affiliated with the University of Melbourne and founded Synchron, the company commercialising this technology.
• Brain-computer interface (BCI) implants have previously required craniotomy (i.e. direct implantation of an electrode into the brain) to be able to directly pick up signals from the brain
• They have developed a Brain-Computer Interface (BCI) device, called Stentrode (i.e. an electrode built into a stent), that could be implanted into a blood vessel overlaying the brain under the skull by sliding it in through a blood vessel in the neck. It appeared to be safe and enabled patients to do hands-free texting, emailing, online banking and shopping, and communicating care needs using their thoughts.
• This research originated in Melbourne and was initially partly supported by MNDRA.

Australian MND Researchers

• Professor Justin Yerbury, a researcher at the University of Wollongong who has MND himself, has continued to receive accolades. In September he received Eureka Prize for Scientific Research and in November he was awarded the Excellence in Medical Biological Sciences Prize in the 2022 NSW Premier’s Prizes for Science & Engineering.
• Professor Matthew Kiernan received the 2022 Ramaciotti Medal for Excellence in October 2022.
• Professor Samar Aoun has been named the 2023 WA Australian of the Year in recognition of her work in research and advocacy for end-of-life care, bereavement and grieving. We are fortunate to have Professor Aoun serve on our board, the MND Australia Research Committee and as President of MND WA. Professor Aoun's research focuses on under-served population groups, such as people with MND, and she strongly advocates for person-centred health and social care. Her work on supporting family caregivers at end-of-life has informed policy and practice at the national and international levels.