Welcome to the MNDRA research update. In this report we will highlight outcomes and advances from the MND research world that have caught our attention over the last few weeks.

MND Research Australia news

• Registration is now open for the 3rd Australian and New Zealand MND Research Symposium in Melbourne on Tuesday 27th and Wednesday 28th of August. Abstracts are still open for submission until Friday, 21^st of June. 
• The ALS/MND Patient Fellows Program is open for applications to attend the International Symposium on ALS/MND in Montreal, Canada, from December 6 to 8. Its mission is “Bringing People with ALS/MND and Caregivers into the Scientific Discourse.” The Patient Fellows Program is open to people diagnosed with ALS/MND, caregivers and ALS/MND gene carriers. 

Other news

• Vale Rob Burrow. Rob Burrow CBE sadly died on 2 June 2024, four and a half years after he was diagnosed with motor neurone disease. Rob was a brilliant rugby league player in the UK and joined with rugby union player Doddie Weir and soccer player Stephen Darby to raise funds and awareness of MND. His best mate, Kevin Sinfield, has done a series of amazing challenges to support MND charities and has contributed to raising the profile of MND in the UK.
• Professor Matthew Kiernan AM FAA FAHMS has been elected as a 2024 Fellow of the Australian Academy of Science, joining the ranks of the nation’s most distinguished scientists. This is further recognition of his standing as one of the preeminent MND researchers in the world. We are honoured to have had Professor Kiernan serve on our Research Committee for almost 20 years, including 5 of those years as Chair.

Clinical Trial news

• Biogen has announced that the European Commission (EC) has granted marketing authorisation under exceptional circumstances of tofersen for the treatment of adults with superoxide dismutase 1 amyotrophic lateral sclerosis (SOD1-ALS). A “marketing authorisation under exceptional circumstances” is recommended when the benefit/risk assessment of a treatment is determined to be positive but, due to the rarity of the disease, it is unlikely that comprehensive data can be obtained under normal conditions of use. This now means that tofersen will likely soon become available in EU countries, pending pricing negotiations. Biogen is exploring the regulatory and reimbursement pathways for tofersen in Australia. Tofersen is currently available to patients in Australia carrying mutations in the SOD1 gene through Biogen’s compassionate access program.  Biogen have committed to keeping this access available until a regulatory decision has been made in Australia.
• Ionis and Biogen announced they are terminating their joint development of BIIB105 (ION541), an investigational antisense oligonucleotide (ASO) for MND based on negative results from the Phase 1/2 ALSpire study. BIIB105 was designed to reduce expression of ataxin-2 (ATXN2) protein. In mice and cell models of MND, reduction of ATXN2 showed good therapeutic benefits. A big hope for ATXN2 was that it might help with TDP-43-driven disease and therefore help most MND patients. However, despite reducing ATXN2 protein levels in patients during the six-month placebo-controlled trial, treatment with BIIB105 did not result in a reduction in levels of plasma neurofilament light chain (NfL), a marker of neurodegeneration and neuronal damage. Additionally, BIIB105 did not demonstrate an impact on clinical outcome measures of function, breathing and strength.
• Arimoclomol is a drug that targets protein misfolding and helps clear protein aggregates and has been shown to be neuroprotective in animal models of MND, with multiple mechanisms of action. Arimoclomol was tested for MND in the ORARIALS-01 trial in Europe and North America but the results have shown the drug did not improve any disease measures compared with placebo. 

Other Research Outcomes

Mitigation of TDP-43 toxic phenotype by an RGNEF fragment in amyotrophic lateral sclerosis models by Droppelmann and others

TDP-43 is a key protein in nearly all cases of MND - but how can we target it? This study from Canada identified other proteins that interact with TDP-43 and looked what happens when you target them instead. They showed that by targeting RGNEF, a protein that binds to TDP-43, they could reduce neuron death in both fly and mouse models of MND caused by high levels of TDP-43. This is still a long way from the clinic, but it is important to keep identifying new options for treatments to feed into the testing pipeline. No single treatment will ever be a total fix for MND, so we need lots of options.

And to finish up, some advice below from the marvellous Dr Nadia Sethi on the ALS Clinical trials and Research Facebook page 

In honor of ALS Awareness Month...

• All mouse studies are not bad.
• All press releases and news articles are not bad.
• All scientific publications are not good.
• The FDA is not hiding treatments so doctors can make money.
• Scientists are not all inherently lazy.
• ALS is not Covid.
• All drugs in bodies are not good. In fact, sometimes medications cause harm, and not just physical harm.
• No single ALS org is to blame for the lack of treatments.
• No single ALS org will likely lead to a single cure for all ALS.
• If there were better treatments for ALS, we'd still need doctors to make a diagnosis, pharmacies to dispense medications, researchers to find the next better drugs, and ways to prevent ALS altogether.

It's how you interpret information that matters. It needs to be sorted through, just like in any other field or industry. It's enormously difficult to face ALS and the reality and pace of the drug development process.

Are there real issues within the points made above? Yes, there are. However, extreme statements in any direction don't help. Also, being a patient patient is really difficult when you don't know what loss of function is coming next or when.