MND Australia Research

pTDP-43 levels correlate with cell type–specific molecular alterations in the prefrontal cortex of C9orf72 ALS/FTD patients | PNAS pnas.org/doi/10.1073/...

Interesting to see microglia changes are seen first then followed by oligodendrocytes and astrocytes - suggests cascade

Rethinking phase 2 trials in amyotrophic lateral sclerosis There is a long history of ALS therapies being promoted on the basis of Phase 2 data, which then fail to translate into meaningful benefits in Phase 3 tria

Rethinking phase 2 trials in amyotrophic lateral sclerosis academic.oup.com/brain/articl...
Well-thought out discussion - basically if you want to run 6-month Phase 2 trials - use biomarkers for your go/no-go decision. If you want to use ALSFRS-R - you need a longer trial

Title: Genetic counsellors: facilitating the integration of genomics into healthcare

Read our new perspective piece published in @mja.com.au. We explore the role of GCs in genomic medicine and current professional challenges. What started as passionate conference discussions has turned into a great perspective piece!

To read the paper: onlinelibrary.wiley.com/doi/10.5694/...

A clinical trial is currently underway to test this compound in ALS patients. The goal is to determine whether restoring sleep can influence the progression of the disease

AML: sleep problems identified as early warning sign Amyotrophic lateral sclerosis (ALS), also known as Charcot’s disease, or Lou Gehrig’s disease, is a severe neurodegenerative disease that leads to progressive paralysis of muscles involved in voluntar...

Characteristic symptoms of MND/ALS are preceded by sleep disturbances
Findings suggest that sleep disorders appear before the onset of motor impairment and respiratory issues

healthcare-in-europe.com/en/news/aml-...
www.science.org/doi/10.1126/...

Blood–brain-barrier-crossing lipid nanoparticles for mRNA delivery to the central nervous system - Nature Materials A lipid-nanoparticle-based formulation incorporating engineered lipids containing a blood–brain-barrier-crossing moiety effectively delivers mRNA to neurons and astrocytes following systemic administr...

A lipid nanoparticle system capable of delivering messenger RNA (mRNA) to the brain via intravenous injection
Better alternative to intrathecal (spinal) injections
Potential for MND gene therapies?
Only tested in mice so far...
www.nature.com/articles/s41...
www.news-medical.net/news/2025021...

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Neurological Alliance Australia (NAA) (MND Australia area member) are advocating for the creation of a Taskforce for Neurological Conditions to urgently address six critical areas of need.
It takes just a few minutes to send an email to your local MP
countusin.good.do/naa/count-us...

Sports-related concussion not associated with long-term cognitive or behavioural deficits: the PROTECT-TBI study Background The cognitive effects of sports-related concussion (SRC) have been the subject of vigorous debate but there has been little research into long-term outcomes in non-athlete populations. Met...

Not specifically MND but the concussion/brain injury association with neurodegeneration is still not finalised

Sports-related concussion not associated with long-term cognitive or behavioural deficits: the PROTECT-TBI study
jnnp.bmj.com/content/earl...

Genetic testing for #ALS #MND should go beyond identifying a single mutation. Even if a known genetic cause is found. A comprehensive analysis provides a clearer understanding of the condition and can help guide care &research efforts. Happy to help in this fantastic project.

Amyotrophic lateral sclerosis represents corticomotoneuronal system failure Several decades have passed since the anterograde corticomotoneuronal hypothesis for amyotrophic lateral sclerosis (ALS) was proposed. The intervening years have witnessed its emergent support based ...

Some challenging ideas - a very well thought out hypothesis;
Amyotrophic lateral sclerosis represents corticomotoneuronal system failure - Eisen - Muscle & Nerve - Wiley Online Library onlinelibrary.wiley.com/doi/10.1002/...

Pridopidine in Amyotrophic Lateral Sclerosis This randomized platform trial investigates whether pridopidine, a sigma-1 receptor agonist, impacted disease progression among patients with amyotrophic lateral sclerosis.

Pridopidine in ALS - HEALEY Platform Trial Outcome
"In this 24-week study, pridopidine did not impact the progression of ALS"
Is 6-months enough to see change? Healey now moving to 9-month trials - hopefully that will produce more definitive outcomes
jamanetwork.com/journals/jam...

CNM-Au8 in Amyotrophic Lateral Sclerosis This randomized, multicenter platform trial investigates the efficacy of CNM-Au8, an oral suspension of catalytically active gold particles, on the disease progression of patients with amyotrophic lat...

CNM-Au8 in ALS - HEALEY Platform Trial outcomes
No significant positive effects.
Government funded EAP underway. Previous trials showed efficacy in longer-term follow-up - Healey only 6-months
Larger Phase 3 trial under consideration and Clene in discussions with FDA
jamanetwork.com/journals/jam...

Trump Tracker: Firings, lawsuits, and U.S. science in chaos Follow President Donald Trump’s impact on U.S. research and science globally

This morning, the National Science Foundation fired 168 probationary employees, effective immediately. The number represents roughly 10% of its workforce.

Follow Science’s coverage of President Donald Trump’s impact on U.S. research and science globally. ⬇️ scim.ag/40XtSSi

We're aware there is still debate going on, on the merits of ellorarxine. We've made our position on this clear, which is that from the data published so far, it is one of many drugs or compounds in a similar position. We'll be watching developments closely, as we do with all such situations.

We are alarmed by proposed funding cuts that would devastate the fight against ALS. Slashing funding for NIH will hinder efforts to turn ALS from fatal to livable and cure it. Congress MUST reject these cuts! We need your voice NOW more than ever. bit.ly/NIH-funding-...

EXPERTS-ALS Accelerating MND Drug Development EXPERTS-ALS Accelerating MND Drug Development You may have seen the recent news from the UK MND Research Institute announcing that one of its first projects, EXPERTS-ALS, funded by the NIHR from th…

How does EXPERTS-ALS fit into the MND global drug development process?

#als #mnd

united2endmnd.org/2025/02/10/e...

#united2endmnd

Our study on the safety and tolerability of Trimetazidine in #ALS @braincomms.bsky.social
Trimetazidine reduced oxidative stress markers and energy expenditure, warranting a follow up study

@rpavaneijk.bsky.social @fredsteyn.bsky.social @ammaralchalabi.bsky.social

academic.oup.com/braincomms/a...

Trump Administration Cuts Put Medical Progress at Risk, Researchers Say Grants from the National Institutes of Health come with additional money for overhead. A planned $4 billion cut would leave colleges with large budget gaps.

“These are real consequences, longer waits for cures and for diagnosis, slower scientific progress, losing out to competitors… and fewer jobs. Those who are facing any health challenges will suffer from less biomedical research.”
— D. Skorton

Via @nytimes: www.nytimes.com/2025/02/07/u...

The NIH’s drastic cut to indirect cost rates is a critical threat to U.S. research infrastructure The drastic reduction in indirect costs is not a path to innovation or cost savings — it’s a threat to U.S.’s position as global leader in medical research.

The NIH’s drastic cut to indirect cost rates is a critical threat to U.S. research infrastructure www.statnews.com/2025/02/08/n... via @statnews.com

Can't do your research in the dark or in the garden - infrastructure funding is vital and much of that comes through indirect costs!

An open-label phase 2a study to assess the safety and tolerability of trimetazidine in patients with amyotrophic lateral sclerosis van Eijk et al. report that oral trimetazidine is safe and well-tolerated in amyotrophic lateral sclerosis (ALS) patients, significantly reducing oxidative

Good to see this Australian-led study ready for the next phase;
Open-label phase 2a study to assess the safety and tolerability of trimetazidine in patients with ALS
academic.oup.com/braincomms/a...
@rpavaneijk.bsky.social @ngoshyuan.bsky.social @fredsteyn.bsky.social @ammaralchalabi.bsky.social

First-in-human study of epidural spinal cord stimulation in individuals with spinal muscular atrophy - Nature Medicine Improved muscle function, strength and fatigue measures were observed after electrical spinal cord stimulation in individuals with spinal muscular atrophy.

With Tofersen having the potentially to significantly slow disease - would such treatments as this potentially return some function if used in conjunction (sorry behind paywall)

First-in-human study of epidural spinal cord stimulation in individuals with SMA
doi.org/10.1038/s415...

New Qalsody Results Bring Hope for Recovery of Lost Function and More Time Evidence is emerging that not only is functional improvement possible, it’s happening for some people with SOD1-ALS who have been treated with Qalsody® (tofersen).

ALSA summary here
www.als.org/blog/new-qal...

Tofersen treatment leads to sustained stabilization of disease in SOD1 ALS in a “real‐world” setting Objective Patients with amyotrophic lateral sclerosis (ALS) caused by superoxide dismutase 1 (SOD1) gene mutations (SOD1 ALS) treated with tofersen have shown slowing of disease progression, and dis...

Only 7 patients but encouraging finding
Currently under review for approval by TGA in Australia
Tofersen treatment leads to sustained stabilization of disease in SOD1 ALS in a “real‐world” setting
onlinelibrary.wiley.com/doi/10.1002/...

Education purposes - they may not even realise they were in the wrong

We are aware of recent discussions within the MND community regarding research into ellorarxine. Read our update here 👇
www.myname5doddie.co.uk/whats-on/art...

I would recommend writing to the authors to ask what permissions they had and what ethics approvals they had in place.

Most people do care Jean - such studies are an exception. This does seem to be a significant breach of trust.
Thankyou for calling it out.

Longer disease progression milestone-free time in people with amyotrophic lateral sclerosis treated versus not treated with intravenous edaravone: results from an administrative claims analysis Aim: To estimate time-to-progression milestones in people with amyotrophic lateral sclerosis (PALS) treated versus not treated with intravenous (IV) edaravone (Radicava® IV, Mitsubishi Tanabe Pharma A...

Plenty of caveats but a decent number of participants and to my non-expert eye a reasonable analysis;
Longer disease progression milestone-free time in people with ALS treated vs not treated with iv edaravone: results from an administrative claims analysis becarispublishing.com/doi/10.57264...

Estimating the minimum important difference in the ALSFRS-R-instrument in people living with MND Objective: The Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) is a commonly used outcome measure in clinical trials for motor neuron disease (MND) therapies. As such, understandin...

Very useful study - would be great to see further studies adding to the data and develop consensus numbers.

Full article: Estimating the minimum important difference in the ALSFRS-R-instrument in people living with MND www.tandfonline.com/doi/full/10....