Huntington’s disease: results of the AMT-130 gene therapy after three years of follow-up

On 24 September 2025, the biotechnology company uniQure (Amsterdam and Lexington, USA) released topline results from its phase I/II studies of AMT-130 (generic name: ifezuntirgene inilparvovec), an investigational gene therapy for Huntington’s disease.

The disease and the therapy

Huntington’s disease is an inherited neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene. It leads to involuntary movements, behavioural changes and cognitive decline. According to the company, there are currently no approved treatments that slow the disease.

AMT-130 is given once, through MRI-guided neurosurgery, directly into the striatum (caudate and putamen). It delivers an RNA molecule (a microRNA) designed to silence the huntingtin gene.

What the data showed

The company analysed 29 treated patients (17 high dose, 12 low dose). At 36 months, the 12 high-dose patients assessed showed 75% slower progression on the composite cUHDRS scale and 60% slower progression on Total Functional Capacity (TFC), compared with similar untreated patients drawn from the Enroll-HD observational registry. The comparison was not with a randomised placebo group, and the number of patients is small.

What has happened since

• November 2025: the company said the US FDA no longer agreed, at that point, that data compared with an external control could be enough as the main evidence for an approval application.
• June 2026: according to the company, the FDA said the 36-month data would be acceptable as the primary basis for an accelerated approval application. On 2 September 2026, uniQure announced it had filed in the US and with the UK regulator (MHRA).
• 29 September 2026: an updated 36-month analysis of 15 high-dose patients showed 80% slowing on cUHDRS. At 48 months (12 patients), slowing was 44% on cUHDRS, not statistically significant, and 61% on TFC; the company believes missing data in the control group affected the result. The company also restated that five high-dose patients had serious side effects related to inflammation of the central nervous system, all of which resolved.

What it means for patients now

AMT-130 is not approved; the announced applications are under review in the US and the UK. Open questions remain about the long-term effect, the safety of a brain procedure and how robust the comparison with an external group is. People affected and their families can discuss these data, and any clinical trials, with their neurologist.