MND Australia and MND Research Australia research news

• The MND research community lost a giant of research and a staunch advocate with the passing of Professor Justin Yerbury on the 28^th July. Refusing to give in to this cruel disease that afflicted him and took many of his family members, Justin forged a brilliant research career leading an amazing team at the University of Wollongong developing new treatments for MND. MND Australia are honoured to have supported Justin's research through his career. He leaves an extraordinary legacy for which the whole MND community are deeply grateful.
• If anyone is interested in contributing to the current government review on the drug approval and reimbursement processes please take a look at this opportunity. This review aims to facilitate the capture of consumer and patient perspectives earlier in the health technology assessment (HTA) process to assist the Pharmaceutical Benefits Advisory Committee and other HTA advisory bodies to obtain an understanding of issues arising from new technologies, innovations and the associated implications for consumers.
• The next Australian and New Zealand MND Research Symposium will take place in Wollongong on the 17^th and 18^th November. Abstract submission is now open and registration will open soon. The meeting will be both face-to-face and streamed via Zoom with attendance free for those with lived experience. 
• Applications for the MNDRA funding round for grants commencing 2024 are now open and applications are welcomed.  Applications close 31st August.

Recent clinical trial developments

SPG302

A clinical trial for a drug called SPG302 is being conducted by Nucleus Network in Melbourne, on behalf of Spinogenix, the US company who make the drug. SPG302 has been developed to increase the number of synapses in nerve cells which are lost in MND. The synapse is the site of contact between two nerve cells, or the nerve cell and muscle, that enable communication via chemical signals and is key for the brain control of muscles for movement. The trial is a Phase 1 trial, which is the first step in testing whether a drug can develop into a viable treatment. It will initially test how the drug behaves in healthy volunteers to check for any toxic effects and how long it lasts in the body. Early next year, there will also be a small part of this study which will test the drug in MND patients, but only for a very short period (4 weeks). You can read more about SPG302 on a recent MND Australia news article. 

Radicava/Edaravone
Mitsubishi Tanabe Pharma America, Inc are the company that manufacturers both the infusion and oral forms of RADICAVA (edaravone). They have been running a large Phase 3B study to evaluate the superiority of a once-daily dosing regimen of oral edaravone vs. the FDA-approved on/off dosing regimen administered in 28-day cycles. An interim analysis has shown that daily oral edaravone is not better than the current 2-weeks on/2-weeks off oral dosing regimen which matches the IV infusion regime. They have therefore discontinued the trial and also the associated expanded access program (EAP).

ALSUntangled

ALSUntangled is a brilliant resource that reviews alternative and off label treatments with the goal of helping people with MND make more informed decisions about them. They recently published a review of Nuedexta as having potential to improve speech, salivation, or swallowing functions. Nuedexta is approved in the US to treat pseudobulbar affect (PBA) and we recently wrote about a short trial testing Nuedexta in MND. ALSUntangled have now undertaken a more comprehensive review and stated they feel there is sufficient evidence to consider Nuedexta treatment for bulbar dysfunction in ALS patients with and without PBA.

International research outcomes

Repeated mild traumatic brain injury triggers pathology in asymptomatic C9ORF72 transgenic mice - by Aydan Kahriman and others

Researchers in the US used a mouse model of MND that carries a C9ORF72 genetic defect. A number of studies have suggested that repeated traumatic brain injury represents a risk factor for FTD and MND, but its role remains unclear. They looked at the effects of mild repetitive traumatic brain injury (rTBI) in this mouse model and showed that rTBI made MND and FTD symptoms worse in this model as well as increasing neuroinflammation and driving cell changes in the brain. This suggests rTBI can be an environmental risk factor that is sufficient to trigger FTD/ALS-associated neuropathology and behavioural deficits. It should be noted though that this is a mouse model and translation to MND patients is considerably more complex. 

Development of a Rasch-Built Amyotrophic Lateral Sclerosis Impairment Multidomain Scale to Measure Disease Progression in ALS - by Adriaan D. de Jongh and others

It is well accepted that although the ALSFR_R scale (Revised Amyotrophic Lateral Sclerosis Functional Rating Scale) is the best we currently have for measuring MND disease progression, it is far from ideal. The ALSFRS-R is multidimensional, meaning that multiple independent facets of ALS disease progression (“dimensions,” i.e., bulbar, motor, and respiratory functioning) are summarized into 1 total score. The fundamental problem is that patients with equal total scores may not be comparable in their disease severity or prognosis. Bulbar-onset and spinal-onset patients, for example, have different disease courses, respiratory insufficiency may occur at any time point, and many patients will never develop bulbar symptoms or weakness in all limbs. A team have instead built the ALS Impairment Multidomain Scale (AIMS) which uses a “Rasch-built scale”. This ensures that weighting is linear and worse answer options progressively become more probable during the course of the disease. AIMS consists of separate bulbar, motor, and respiratory subscales that have high test-retest reliability, are optimized to measure disease progression, and are strongly related to survival time. The AIMS can be easily administered and may increase the likelihood of identifying effective treatments in ALS clinical trials.