Single-dose genetic medicine halts the progression of ALS and frontotemporal dementia in mice

Neuroscientists at Macquarie University in Australia have developed a single-dose genetic medicine that has been proven to halt the progression of both ALS and frontotemporal dementia (FTD) in mice – and may even offer the potential to reverse some of the effects of the fatal diseases.

It may also hold opportunities for treating more common forms of dementia, such as Alzheimer's disease.

The new treatment, dubbed CTx1000, targets pathological build-ups of the protein TDP-43 in cells in the brain and spinal cord, which has been It has been associated with ALS, FTD and other forms of dementia.

The Macquarie University research team, led by Professor Lars Ittner, hopes to see CTx1000 begin human clinical trials in as little as two years.

Cells like neurons produce TDP‑43 naturally, and it is important for their healthy function. Under certain conditions, it accumulates in the wrong part of the cells, clogging them and preventing them from working properly. 

For the past 15 years, Professor Ittner and his team have been researching pathological TDP-43 build‑up.

Professor Ittner says in their latest findings, have discovered for the first time that where there is pathological TDP‑43, there is also an increase in a second protein, 14‑3‑3.

"The two proteins interact, resulting in these build-ups in the cells," he says.

"From this, we were able to isolate a short peptide that controls this interaction, and that's what we used to create CTx1000.

"When we administered it in the lab, it dissolved the build-ups, tagging TDP-43 proteins for recycling by the body, and prevented new ones from forming.

"Importantly, CTx1000 targets only pathological TDP-43, allowing the healthy version of the protein to be produced and go about its work unhindered."

Professor Ittner says this makes CTx1000 incredibly safe, and they have seen no adverse effects in their studies.

Lead author of the paper, Professor Yazi Ke, says in lab conditions, CTx1000 stopped ALS and FTD from progressing even at very advanced stages, and resolved the behavioural symptoms associated with FTD.

"We have great hopes that when this progresses to human trials, it will not only stop people from dying from both ALS and FTD, but even allow patients to regaining some of the lost function through rehabilitation," she says.

CTx1000 is one of the key discoveries being championed by Celosia Therapeutics, a Macquarie University spin-out company formed in 2022 to help bring the groundbreaking work of the University's neuroscientists from the lab to patients.

Celosia Therapeutics is actively seeking investment to facilitate CTx1000 to progress to clinical trial stage.

About ALS and FTD

Also known as motor neuron disease (MND), ALS causes the progressive loss of the neurons that allow the brain and spine to communicate with the muscles.

In its early stages, patients experience muscle weakness, but as the disease progresses, they gradually lose the ability to walk, speak, swallow and breathe unaided. Most people with ALS die within two to five years of diagnosis.

While there is a genetic therapy showing promise for one form of familial ALS, there are few treatments available for the sporadic ALS that makes up 90 per cent of all cases.

Of those, the most effective can only extend a patient's life by up to five months. All require frequent doses, and some come with side effects that are difficult to cope with.

FTD is one of the rarer forms of dementia, but it is the second-most common form in people younger than 65. Actor Bruce Willis was diagnosed with FTD in 2023.

It does not always have obvious physical symptoms, but it results in cognitive decline coupled with behavioural symptoms including anxiety, loss of inhibition, personality change, and impaired judgment. Patients may live for more than 10 years after diagnosis, but it is ultimately fatal.

There is currently no treatment for FTD.