An Australian-developed therapy aimed at halting motor neurone disease progression and restoring function is advancing to a national Phase 2 clinical trial, following encouraging earlier results developed from research at The University of Queensland’s Queensland Brain Institute.
Targeting EphA4 Receptors
The 75-participant trial is advanced by clinical-stage biotechnology company NuNerve, which was established by UQ commercialisation company UniQuest and the Estate Peter Goodenough Unit Trust. The program builds on more than 25 years of research originating at QBI by Emeritus Professors Perry Bartlett and Andrew Boyd.
NuNerve Chair Emeritus Professor Perry Bartlett AO explained that the protein-based therapy, named NUN-004, is designed to inhibit EphA4. Excessive signalling by this receptor has been linked to motor neuron degeneration and impaired recovery of nerve connections.
No approved treatment has been shown to halt or reverse progression across the broad MND population,
Emeritus Professor Perry Bartlett AO, NuNerve Chair
Professor Bartlett noted that current treatments largely focus on slowing the loss of function. NUN-004 was designed to go further to protect motor neurons and create the conditions for damaged neural connections to repair, according to News Medical.
We have spent more than 25 years following the biology of EphA4, from understanding its role in motor neuron connections to developing a therapy that can now be tested rigorously in people living with MND.
Emeritus Professor Perry Bartlett AO, NuNerve Chair
Trial Design Across Six Sites
Motor neurone disease, also known as amyotrophic lateral sclerosis, is a progressive neurological condition affecting nerve cells in the brain and spinal cord responsible for movement. As these motor neurons deteriorate and die, the brain can no longer send signals to muscles, leading to weakness, wasting, and loss of function over time.
The trial will recruit 75 participants across six Australian clinical sites located on the Sunshine Coast, Sydney, Newcastle, Brisbane, and Perth. Participants will be randomised two-to-one to receive either NUN-004 or a placebo for a 24-week double-blind study. This will be followed by a 24-week open-label extension where all participants receive NUN-004.
Researchers will assess change in the ALS Functional Rating Scale-Revised, safety, and tolerability, alongside respiratory, neurophysiological, quality-of-life, and biomarker measures. NuNerve Clinical Lead Associate Professor Antony Winkel stated that the study was carefully designed to evaluate treatment effects.
This trial combines measures of everyday function with respiratory, neurophysiological and biomarker assessments to determine whether the early Phase I signal is a real treatment effect,
Associate Professor Antony Winkel, NuNerve Clinical Lead
NuNerve Clinical Lead Associate Professor Antony Winkel also emphasized the critical nature of the trial for patients, noting that individuals living with motor neurone disease urgently require better treatment options grounded in high-quality evidence.
Professor Winkel added that confirming these findings would represent an important result for people living with the condition and place Australian motor neurone disease research firmly on the international stage.
The new evaluation follows a published Phase I/Ib study involving 20 healthy volunteers and eight people living with MND. That initial study showed NUN-004 was well tolerated, with disease stabilisation observed during treatment and participants reporting improvements in grip, balance, walking, strength, and reduced fatigue.
UniQuest Supports Long-Term Research Translation for NuNerve
UniQuest CEO Dr Dean Moss highlighted the significance of reaching this stage of clinical translation.
This is a powerful example of what research translation looks like over the long term, with more than 25 years of UQ discovery now progressing through a company created to take that science forward,
Dr Dean Moss, UniQuest CEO
Dr Moss expressed pride in the role UniQuest played in helping establish NuNerve and supporting a pathway for this long-term scientific discovery to be rigorously tested in people living with motor neurone disease.
NuNerve intends to seek international investment and partnerships to progress NUN-004 into Phase 3 and toward potential regulatory approval in major global markets.
