A GROUNDBREAKING Phase I/II clinical trial has reported that AMT-130, the first gene therapy tested in Huntington’s disease, slowed progression of the condition by 75% compared to a matched cohort, marking the most significant advance in the field to date.
Revolutionary trial design puts gene therapy to the test
Huntington’s disease is a fatal neurodegenerative disorder caused by a single genetic mutation, with no proven treatments to delay decline. The trial, led by University College London (UCL) investigators, tested AMT-130 in 29 patients who underwent direct brain infusion via stereotactic neurosurgery. Outcomes were compared with participants in Enroll-HD, a large natural history study. After 36 months, patients receiving a high dose of AMT-130 showed markedly slower decline on the composite Unified Huntington’s Disease Rating Scale (UHDRS), alongside improvements on the Total Functional Capacity (TFC) scale and multiple motor and cognitive measures.
Gene therapy shows tangible neuronal protection
In addition to clinical outcomes, the study assessed neurofilament light chain (NfL) levels, a biomarker of neuronal injury. Treated patients showed reductions in NfL, in contrast to the 20–30% rise typically seen over three years, suggesting AMT-130 modifies the underlying disease process. The therapy was generally well tolerated, with a manageable safety profile. Investigators emphasised that a single dose could provide lifelong benefit by permanently silencing production of toxic huntingtin protein within vulnerable neurons.
Next steps could transform Huntington’s treatment
Researchers plan to submit regulatory applications for accelerated approval in the USA, with Europe and the UK to follow. Experts describe the results as a potential turning point, with broader implications for gene therapy in other neurodegenerative conditions.
“Trial results come through in numbers and graphs, but behind each datapoint is an incredible patient who volunteered to undergo major neurosurgery to be treated with the first gene therapy we’ve ever tested in Huntington’s disease. That is an extraordinary act of bravery for the benefit of humanity,” said Ed Wild, principal investigator of the UCL Huntington’s Disease Centre trial.
If confirmed in larger studies, AMT-130 could become the first licensed therapy to meaningfully slow Huntington’s disease, offering patients and families new hope against this devastating disorder.
Reference
UCL. Gene therapy appears to slow Huntington’s disease progression. 24 September 2025. Last accessed: 25 September 2025. Available at: https://www.ucl.ac.uk/news/2025/sep/gene-therapy-appears-slow-huntingtons-disease-progression
