EHDN Chair Patrick Weydt (University of Bonn) and Deputy Chair Åsa Petersén (Lund University) share the excitement of the Huntington’s disease (HD) community in welcoming the topline results from uniQure’s phase 1/2 study of the experimental gene therapy AMT-130, which aims to lower the production of huntingtin. While the hopes of the community are high, the results are complex and thus need to be communicated with care.

Topline Results: 24 September 2025
On 24 September 2025, uniQure announced that the phase 1/2 study of AMT-130 met its prespecified primary endpoint, with the high dose demonstrating a statistically significant slowing of disease progression as measured by the composite Unified Huntington’s Disease Rating Scale (cUHDRS) at 36 months compared to a propensity score-matched external control (Enroll-HD data). More specifically, treated patients had a mean change in cUHDRS from baseline of -0.38 compared to a change of -1.52 for patients in the propensity score-matched external control, representing a slowing of disease progression by 75% over a 3-year period.
The study also met a key secondary endpoint by achieving statistically significant slowing of disease progression as measured by Total Functional Capacity (TFC) at 36 months compared to a propensity score-matched external control. Treated patients had a mean change in TFC from baseline of -0.36, compared to a change of -0.88 for patients in the propensity score-matched external control, representing a 60% slowing of disease progression.
Favourable trends were reported for other secondary endpoint measures of motor and cognitive function, alongside a mean reduction from baseline in cerebrospinal neurofilament light protein of -8.2%, a biomarker of neurodegeneration in HD.
Combined, these topline results provide important proof of concept that HD is a modifiable disease.

Who Was Involved?
The study took place at sites across the US and Europe, with AMT-130 in Europe being delivered by neurosurgical teams in Cardiff and Vale University Health Board and Cardiff University, and the Interventional Neurotherapy Center (INC) in Warsaw. Ralf Reilmann of the George Huntington Institute (GHI) in Münster, Germany, was part of the team that helped develop this pioneering intervention, and Sarah Tabrizi from University College London (UCL) served as the lead scientific advisor.

What We Don’t Yet Know
While these results are positive, it is important to remember that these are preliminary, topline results from an early-stage clinical trial in a small number of highly selected patients. We should also note that the current trial was not blinded (meaning that placebo effects cannot be ruled out) and that while the use of external controls is a valid methodology, it does have limitations. In addition, we do not yet know the outcomes of other measures completed as part of the clinical trial. As such, we look forward to the release of further analyses and the peer-reviewed publication of the findings.

Critical Next Steps: #hopebutstayreal
The topline results from uniQure’s phase 1/2 study of AMT-130 bring significant hope to all those impacted by HD. This is an important step forward for HD, but it is only the beginning of a journey. The intervention is not yet available outside of a clinical trial. As the results are preliminary, if a regulatory licence is granted, then further research will almost certainly be required. Fortunately, EHDN is well-positioned to support this process. In particular, if the regulatory authorities license AMT-130, it will be important to find ways to simplify the surgery (which currently takes many hours) in order to make the treatment more widely available. EHDN chair emeritus Anne Rosser explains, ‘As this news broke, several of us were at an EHDN Advanced Therapies neurosurgical delivery workshop in Venice, so we are already working on solutions to the delivery of such therapeutics. The EHDN Advanced Therapies Working Group has been working on the broad translational challenges for gene and cell therapies for years, and the EHDN HEATED (Huntington’s Equal Access to Effective Drugs) Task Force has been discussing how to address the challenges of integrating new therapies into clinical practice.’

The latest developments in HD research inspire us to work even harder to support further studies of AMT-130 and other therapies in the drug development pipeline.

Patrick Weydt
Åsa Petersén