MND Australia

Research Directions | April 2023

MND Australia and MND Research Australia research news

  • The MNDRA State of Play webinar series has commenced for 2023. The next webinar is titled “Can we target the muscle to develop treatments for MND?” and features 2023 MNDRA Innovator Grant recipients A/Prof Peter Noakes & Prof Aaron Russell. Tuesday, 18 April @ 7pm AEST. Sign up here
  • State of Play has been running since 2021. If you missed previous episodes, recordings are available here

Recent clinical trial developments


  • The pharmaceutical company Biogen have developed a treatment specifically for those carrying SOD1 mutations.
  • The US FDA are currently considering this drug for approval. A key stage of this consideration is a meeting of an Advisory Committee (AdComm), which is a team of experts that considers the evidence provided by Biogen and provides non-binding recommendations to the FDA regarding approval.
  • The AdComm recommended that the neurofilament light (NfL) biomarker works well as a measure of MND disease and also that the treatment, tofersen, should be approved under the conditional “Accelerated Approval” program. This will mean the drug will become available but Biogen need to keep monitoring the effects of the drug in further studies. A final decision is expected later this month.


  • Clene, a small pharmaceutical company, reported further results from the open-label extension (OLE) RESCUE Phase 2 trial for their treatment, CNM-Au8.
  • CNM-Au8 treatment was well-tolerated without long term safety concerns. 
  • Data has been collected up to 120 weeks which showed a significant preservation of function (ALSFRS-R) during the long-term open-label extension (OLE) from week 24 to 120 weeks from randomisation, as well as a reduced risk of ALS clinical worsening (death, feeding tube insertion or initiation of ventilator support) of 52% over the 120 weeks.
  • We are currently waiting to hear Clene’s next step for this treatment with respect to approval applications or further trials.

“The open-label data at 48 weeks and through 120 weeks from randomization suggests that CNM-Au8 has the ability to meaningfully improve patient daily functional status over longer periods of time, together with sustained treatment effects on ALS disease progression and survival,” stated Professor Matthew Kiernan, one of the trial’s clinical advisors.

COYA 302

  • Coya Therapeutics is a biotechnology company developing treatments focused on the biology and potential therapeutic advantages of regulatory T cells (“Tregs”) to target neuroinflammation. They have developed a treatment where cells are extracted from the patient then manipulated to boost the levels of anti-inflammatory Tregs before injecting them back into the patient. 
  • They conducted a proof-of-concept open-label study which evaluated the safety and tolerability, function of Tregs, biomarkers, and preliminary efficacy (as measured by the ALSFRS-R scale) of their treatment, COYA 302, over 48 weeks.
  • This study was conducted in four MND patients at the Houston Methodist Hospital in the US. COYA 302 appeared to be well tolerated in all study patients.
  • The results showed no decline or minimal decline at 24 and 48 weeks indicating significant amelioration in the progression of the disease.
  • Over the course of treatment, COYA 302 significantly lowered serum biomarkers of inflammation and oxidative stress.

“We believe the results of this initial proof-of-concept study in a small number of ALS patients are encouraging and warrant conducting a larger and controlled industry-sponsored study,” Adrian Hepner, M.D., Chief Medical Officer of Coya commented. “We plan to file an IND with the FDA in the second half of 2023 and initiate a clinical study soon thereafter” (An IND is an Investigational New Drug Application).


  • Prilenia Therapeutics, a small biotechnology company targeting neurodegenerative diseases, recently completed a Phase 2 trial of their drug Pridopidine as part of the Healey Platform Trial in the US.
  • The Healey Platform trial allows multiple treatments to be tested in parallel while sharing clinical resources and the placebo group, greatly reducing the chance of patients receiving placebo as well as making trials much cheaper to run.
  • This drug targets the sigma-1 receptor which is highly expressed in the brain and spinal cord and is thought to regulate bulbar, speech and limb function. No safety issues were identified. 
  • In the 24-week trial no statistically significant differences in ALSFRS-R, muscle strength or respiratory function were seen between treatment and placebo groups. There were some improvements in a subset of patients within 18-months of symptom onset with a 40% reduction neurofilament light (NfL) levels also seen in this subgroup.
  • Improvements in speech function were seen.

“The positive results on speech and bulbar function, and on overall function and breathing in people earlier in disease course, are very encouraging and deserve further investigation in a phase III trial. Those are sensitive measures of disease progression and may indicate a general benefit of pridopidine that we were not able to detect in this study," said Merit Cudkowicz, principal investigator.

Australian research discoveries

Pathologically mislocalised TDP-43 in upper motor neurons causes a die-forward spread of ALS-like pathogenic changes throughout the mouse corticomotor system - by Laura Reale from Catherine Blizzard’s team at the University of Tasmania

  • The origin of pathogenesis (disease development) in ALS is unknown. Two hypotheses exist: dying-forward (brain → spinal cord) and dying-backward (spinal cord → brain).
  • By experimentally expressing adapted TDP-43 (a binding protein that aggregates in MND) in the brain, this team was able to investigate the dying-forward hypothesis.
  • Producing TDP-43 in the brain caused a spread of pathogenic changes through connections to the spinal cord and some of the lower motor neurons were affected depending on their exact location. These lower motor neurons could be protected in regions where inhibitory proteins were increased.
  • This supports the dying-forward (brain → spinal cord) hypothesis of playing a significant role in MND
  • This work was partially funded by MNDRA

Use of hip- versus wrist-based actigraphy for assessing functional decline and disease progression in patients with motor neuron disease - by Cory Holdom from Shyuan Ngo’s and Derik Steyn’s group at the University of Queensland

  • Actigraphy is the measurement of activity/movement using a small body sensor such as a smart watch. This study looked at whether such devices can be used to track functional decline and disease progression in MND. They also compared the utility of wrist- and hip-based actigraphy for assessing functional decline in patients.
  • They showed the use of wrist actigraphy mirrored decreased activity in patients compared to controls.  However hip-based measurements had stronger correlations with disease progression whereas wrist-based measurements correlated with decline in fine-motor function.
  • This showed that this approach has promise but more work needs to be done to reliably interpret the information provided in relation to MND progression.