Australian patients could soon be among the first in the world to trial a single-dose injection to halt and potentially reverse some symptoms of motor neurone disease and frontotemporal dementia, after researchers in Sydney discovered a way to clear blockages linked to both diseases in mice.
Abnormal clusters of a protein called TDP-43 are a common feature of many neurodegenerative diseases, including motor neurone disease (MND), frontotemporal dementia (FTD), and Alzheimer’s.
Dr Annika van Hummel, Professor Yazi Ke, and Professor Lars Ittner are part of the research team at Macquarie University who have been searching for ways to treat MND and frontotemporal dementia for 15 years.Credit: Samantha Christensen
Patients with MND lose muscle strength in the early stages before gradually losing the ability to walk, talk, swallow and breathe. Most die within five years of diagnosis.
FTD is the name given to the group of disorders that occur when cells in the frontal and temporal lobes of the brain are lost. Although rare, it is the second-most common form of dementia in people younger than 65. Actor Bruce Willis was diagnosed with FTD in 2023, aged 68.
After 15 years of investigating ways to break down or prevent these clusters from forming, Professor Lars Ittner and his team of neuroscientists at Macquarie University have developed a single-dose genetic medicine that can halt the progress of both MND and FTD in mice.
Ittner said the most surprising part of the research, published in the international neuroscience journal Neuron on Friday, was that some of the mice even regained strength and improved motor performance, suggesting that dissolving the protein clusters was helping return normal function to the affected neurons.
“The hope is that you’re not only stopping the disease, which sometimes has already progressed to really bad state, but actually, you can regain some functions,” he said. “It will not be a miracle, but … regaining some minor neurological function can make a big impact for patients.”
A start-up company spun out of the research, Celosia Therapeutics, will now seek funding and regulatory approval to take the research to human trials within two years.
Also called amyotrophic lateral sclerosis (ALS), MND causes the loss of neurons that facilitate communication between the brain, spine and muscles.
The TDP-43 protein helps to regulate gene expression and is normally found in the nucleus of brain cells, but under certain conditions can accumulate in parts of cells outside the nuclei, preventing them from working as they should.
Ittner and his team were the first to discover the protein was essentially clumping around another protein (called 14-3-3) outside the nucleus. The researchers then developed a medicine that acts as a “vacuum cleaner”, breaking up the clumps and allowing the TDP-43 protein to return to the nucleus where it can perform its normal function.
Professor Matthew Kiernan, a neurologist and chief executive officer of Neuroscience Research Australia (NeuRA), said the research was “excellent science” but cautioned that there was still a long way to get it into the clinic.
He said there had been more than 150 positive animal trials for treating MND, but none of those had so far found success in human trials.
“There’s no naturally occurring ALS or MND in any animal – it’s a uniquely human disease,” he said. “Trials in animals are successful and show promise, but it’s yet to be translated to humans.”
Ittner said the difference with their study was that they tested four different ways that TPD-43 could form to produce MND and FTD symptoms. They also treated mice who already had symptoms, whereas many other studies had treated them before they were symptomatic.
“This is closer to the clinical setting, where patients see the doctor when symptoms have become apparent and disease has already progressed,” he said.
The research was funded by grants from the National Health and Medical Research Council and MND Australia.
Fight MND, the charity co-founded by former AFL player and coach Neal Daniher, has committed $1.2 million towards the next phase of trials.
Start the day with a summary of the day’s most important and interesting stories, analysis and insights. Sign up for our Morning Edition newsletter.