AMT-130 Gene Therapy Slows Huntington Disease Progression by 75 Percent

A global clinical trial for a groundbreaking Huntington’s disease treatment has posted positive results, marking the first time a drug trial has reported continuing, statistically significant slowing of the fatal hereditary disorder. Researchers found that patients receiving a high dose of the experimental gene therapy experienced 75 per cent less disease progression overall compared to a matched cohort of untreated individuals from a long-running natural history study.

uniQure and UCL Trial Data Reveal 75 Per Cent Slowing Over 36 Months

The experimental treatment, developed by gene therapy company uniQure, involves a single dose injected straight into the brain to reduce levels of toxic proteins. The findings were announced as 29 patients completed up to 36 months of a Phase I/II clinical trial. Among them, 12 participants received a high dose of the drug and completed the full 36-month follow-up period, according to data highlighted by scientists at University College London.

To evaluate efficacy, the researchers compared trial participants against an external cohort from Enroll-HD, a long-running natural history study. This comparison predicted the extent of functional and cognitive decline expected under standard care. The high-dose group demonstrated statistically significant benefits across the composite Unified Huntington’s Disease Rating Scale—which incorporates motor, cognitive, and functional measures—alongside improvements in Total Functional Capacity and three additional motor and cognitive assessments.

“l am thrilled that this study of AMT-130 showed statistically significant effects on disease progression at 36 months. These groundbreaking data are the most convincing evidence in the field to date and underscore the disease-modifying effect in Huntington’s disease, where an urgent need persists.”

Professor Sarah Tabrizi, lead scientific advisor on the trial at UCL Huntington’s Disease Research Centre, UCL Queen Square Institute of Neurology, and UK Dementia Research Institute at UCL, via UCL

Biomarkers and Neurofilament Levels Point to Modified Disease Course

Beyond functional rating scales, the clinical evaluation measured levels of neurofilament light protein (NfL), an established biomarker released into spinal fluid when neurons suffer injury. In healthy individuals or untreated patients, NfL levels typically rise steadily over time as neurodegeneration advances. By contrast, scientists found that NfL levels in treated patients were lower than at the trial’s outset, running counter to the expected 20 to 30 per cent increase over three years.

uniQure May Seek UK Approval for AMT-130 Gene Therapy Amid FDA Talks

This biological shift suggests that neuronal damage was actively slowed. Investigators reported that AMT-130 maintained a manageable safety profile and was generally well-tolerated by study volunteers, who underwent major neurosurgery to receive the therapy.

“This result changes everything. On the basis of these results it seems likely AMT-130 will be the first licensed treatment to slow Huntington’s disease, which is truly world-changing stuff.”

Professor Ed Wild, principal investigator of the UCL Huntington’s Disease Centre trial site at UCL and UCLH, via UCL

Regulatory Next Steps and Independent Expert Perspectives

Following the 36-month data release, uniQure plans to submit an application to the US Food and Drug Administration requesting accelerated approval to market the drug, with subsequent filings planned in the United Kingdom and Europe. Huntington’s disease is caused by a single genetic mutation on the HTT gene, which orders cells to manufacture a toxic version of the huntingtin protein. The fatal condition affects roughly 8,000 people in the UK and forms part of an estimated 75,000 cases across the European Union, UK, and United States combined, according to corporate figures.

Independent specialists greeted the news with cautious optimism, noting that previous therapeutic candidates have shown early promise only to stumble in later evaluations. Similarly, Roger Barker, a professor of clinical neuroscience at the University of Cambridge, pointed out that larger studies with more participants will be required to confirm the drug’s long-term efficacy across the broader patient population.