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

Neuroscientists at Australia's Macquarie University have developed a single-dose genetic drug that has been shown to halt the progression of both ALS and frontotemporal dementia (FTD) in mice. It may even offer the possibility of reversing some of the effects of the deadly disease. .

There may also be an opportunity to treat more common dementias, such as Alzheimer's disease.

The new treatment, called CTx1000, targets the pathological accumulation of the protein TDP-43 in cells of the brain and spinal cord, which is thought to be associated with ALS, FTD, and other dementias.

The Macquarie University research team, led by Professor Lars Ittner, hopes to begin human clinical trials of CTx1000 within two years at the earliest.

Cells such as neurons naturally produce TDP‑43 and it is important for healthy cell function. Under certain conditions, it can accumulate in the wrong parts of cells, causing them to become clogged and unable to function properly.

For the past 15 years, Professor Ittner and his team have been studying pathological TDP-43 accumulation.

Professor Ittner says the latest findings are the first to discover that where pathological TDP‑43 is present, a second protein, 14‑3‑3, is also increased.

“The two proteins interact, resulting in this accumulation within the cell,” he says.

“From this, we were able to isolate a short peptide that controls this interaction, which we used to create CTx1000.

“When administered in the lab, it dissolved the buildup, tagged the TDP-43 protein so it could be recycled by the body, and prevented new protein from forming.

“Importantly, CTx1000 targets only the pathological TDP-43, allowing the healthy version of the protein to be produced and continue its work unhindered.”

Professor Ittner says this makes CTx1000 incredibly safe, with no adverse effects seen in the study.

Professor Yazi Ke, lead author of the paper, said that in a laboratory setting, CTx1000 halted the progression of ALS and FTD, even at very advanced stages, and resolved the behavioral symptoms associated with FTD.

“We have high hopes that if this progresses to human trials, it will not only stop people dying from both ALS and FTD, but also allow patients to regain some of the lost function through rehabilitation.” ,” she says.

CTx1000 is a key technology backed by Celosia Therapeutics, a Macquarie University spin-out company established in 2022 to bring the university's neuroscientists' ground-breaking research from the lab to patients. This is one of my discoveries.

Celosia Therapeutics is actively seeking investment to advance CTx1000 into clinical trials.

About ALS and FTD

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

In the early stages, patients experience muscle weakness, but as the disease progresses, they gradually lose the ability to walk, talk, swallow, and breathe on their own. Most people with ALS die within 2 to 5 years of diagnosis.

Although there is promising gene therapy for one form of familial ALS, there are few treatments available for sporadic ALS, which accounts for 90% of all cases.

The most effective of them are only able to extend the life of the patient by up to 5 months. All require frequent dosing and some have side effects that are difficult to manage.

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

Although there are not always obvious physical symptoms, cognitive decline occurs along with behavioral symptoms such as anxiety, loss of inhibitions, personality changes, and poor judgment. Patients may live for more than 10 years after diagnosis, but death may occur eventually.

There is currently no cure for FTD.