A gene therapy developed by uniQure appears to slow progression of Huntington’s disease, according to data from a global Phase 1/2 trial led by UCL scientists. The trial results, announced on Wednesday (September 24), show that patients receiving a high dose of AMT-130 experienced 75% less disease progression over three years compared to a matched external cohort.

Huntington’s disease is a fatal neurodegenerative condition caused by a single gene mutation. Symptoms, which usually begin in mid-adulthood, affect movement, cognition and behaviour. About 8,000 people in the UK currently live with the disease, which typically lasts around 20 years from symptom onset. Until now, there have been no treatments shown to slow disease progression.

AMT-130 is a one-time gene therapy delivered directly into the striatum of the brain using stereotactic neurosurgery. The therapy introduces DNA encoding RNA designed to bind and destroy the RNA that produces mutant huntingtin protein, permanently reducing production of the toxic protein. The therapy is expected to last a patient’s lifetime.

In the trial, 29 patients completed up to 36 months of follow-up, including 12 who received a high dose and have full three-year data. Progression was measured using the composite Unified Huntington’s Disease Rating Scale and Total Functional Capacity, with additional assessments of motor and cognitive function. Patients receiving AMT-130 also showed lower spinal fluid levels of neurofilament light protein, a marker of neuronal injury, suggesting reduced neuronal damage.

Professor Sarah Tabrizi, lead scientific advisor on the trial, said: “I 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. For patients, AMT-130 has the potential to preserve daily function, keep them in work longer, and meaningfully slow disease progression.”

Professor Ed Wild, principal investigator at UCL, added: “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. If that happens, we need to work hard to make it available to everyone who needs it, while working no less diligently to add more effective treatments to the list.”

The therapy was generally well-tolerated, with a manageable safety profile. uniQure plans to submit an application to the US FDA early next year for accelerated approval, with applications in the UK and Europe to follow. The results will be formally presented at the HD Clinical Research Congress in Nashville next month.