Gene Therapy Slows Huntington’s Disease Progression by 75%

The gene therapy company uniQure has announced top-level data from its trial of AMT-130, a new gene therapy designed to treat Huntington’s disease.

How AMT-130 targets Huntington’s disease

Huntington’s disease is a progressive neurodegenerative disorder caused by a mutation in the huntingtin (HTT) gene.

The mutation leads to the production of a faulty huntingtin protein and damage to nerve cells, resulting in physical and emotional symptoms including uncontrolled movements (chorea), loss of coordination, difficulty swallowing, mood swings, depression and irritability.

Globally, an estimated 4.88 per 100,000 people suffer from Huntington’s, for which there is currently no cure.

uniQure’s drug AMT-130 is a novel gene therapy that requires a single administration. It uses an adeno-associated virus vector to deliver an artificial microRNA into the brain, which is designed to silence the huntingtin gene and inhibit the production of faulty huntingtin protein.

uniQure has announced that a Phase 1/2 study of AMT-130 met its prespecified primary endpoints based on topline data analysis.

Data from 29 of the trial patients treated with AMT-130 (17 receiving a high dose, 12 receiving a low dose) was analyzed at 36 months post-treatment. Each dose group’s outcomes were compared with a propensity score–matched external control derived from the Enroll-HD natural history dataset (940 for high dose and 626 for low dose), as had been agreed with the FDA.

Patients receiving a high dose of AMT-130 demonstrated a 75% slowing of disease progression as measured by the composite Unified Huntington’s Disease Rating Scale (cUHDRS).

"This is incredible news for everyone affected by Huntington's, a cruel and devastating disease,” said Professor Siddharthan Chandran, director of the UK Dementia Research Institute. “For the first time, we have a drug that slows down Huntington's progression, with people on the treatment showing 75% slower disease progression over the 36-month study.”

AMT-130 also achieved a statistically significant 60% slowing of Hungtington’s disease progression as measured by as measured by Total Functional Capacity.

According to uniQure, AMT-130 achieved positive outcomes across other measures of motor and cognitive function, including:

• 88% slowing of disease progression as measured by the Symbol Digit Modalities Test
• 113% slowing of disease progression as measured by the Stroop Word Reading Test
• 59% slowing of disease progression as measured by Total Motor Score

Patients treated with AMT-130 also showed an average 8.2% drop in cerebrospinal fluid neurofilament light protein (CSF NfL), a biomarker of nerve cell damage. Higher CSF NfL levels are associated with more severe symptoms in Huntington’s disease.

uniQure believes that AMT-130 delivers a dose-dependent response based on the “consistently favorable results in functional, motor and cognitive endpoints at 36 months observed in the high dose group, compared to the variable trends observed in the low dose group”, the press release reads.

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Discussing the drug’s safety in the same release, uniQure said AMT-130 was generally well tolerated and had a “manageable safety profile at both doses”. At the point of data analysis in June 2025, no serious adverse events were observed since December 2022.

Hopeful early findings, but key questions remain

This announcement is likely to generate significant optimism within the Huntington’s disease patient and research communities. However, further studies are required to confirm both the safety and the efficacy of the drug before it can become a viable treatment option.

“The early-stage trial uniQure has reported involves a modest number of patients and much of the control data were not from placebo-controlled patients but from existing natural history data of Huntington’s disease patients,” cautioned Dr. David Rubinsztein, professor of Molecular Neurogenetics and deputy director of the Cambridge Institute for Medical Research. “The results that were reported are from the high-dose group which comprised 17 patients, 12 who were followed up for 36 months. No data were reported from the low-dose group but the impression from the press release was that no significant benefits were seen with the low dose (which is fine if the high dose works and is well-tolerated).”

“The analyses that have been reported are exciting as they suggest a clear slowing of disease progression measured with a range of tools along with a suggestion amelioration of neurodegeneration. While these headline results are from a press release and not from a publication where all the data and analyses can be seen, this provides real hope for this devastating disease,” he added.

Rubinsztein noted that, if successfully validated, uniQure’s approach could have far-reaching implications, potentially reducing levels of other toxic proteins implicated in dementias, certain forms of Parkinson’s disease and motor neuron diseases.

Dr. Roger Barker, professor of Clinical Neuroscience at the University of Cambridge, expressed caution about the therapy’s potential uptake even if trials prove successful: “The trial involves injecting the therapy directly into the brain using a special technique into the striatum on each side of the brain – so its widespread adoption across neurological centres will not be straightforward if it is shown to truly work.”

uniQure said it is eager to discuss the data with the FDA at its pre-Biologics License Application (BLA) meeting expected later this year. The company has set a goal of submitting a BLA in the first quarter of 2026.