The Phase 1/2 study of AMT-130, the first in-human gene therapy designed to slow the course of Huntington’s disease (HD), has announced positive topline results from its pivotal trial.1
The data provide hope that a intrastriatal adeno-associated virus (AVV)-based therapy can meaningfully alter disease trajectory, moving beyond symptomatic management.
Key findings at 36 months1
Primary endpoint met:
- High-dose AMT-130 demonstrated a statistically significant 75% slowing of disease progression on the composite Unified Huntington’s Disease Rating Scale (cUHDRS) versus a propensity score-matched external control (p=0.003).
- Mean cUHDRS decline: –0.38 in treated patients vs –1.52 in controls.
Secondary endpoints:
- Total Functional Capacity (TFC): 60% slowing (–0.36 vs –0.88; p=0.033).
- Cognition & motor outcomes:
- Symbol Digit Modalities Test (SDMT): 88% slowing (–0.44 vs –3.73; p=0.057).
- Stroop Word Reading Test (SWRT): 113% slowing (+0.88 vs –6.98; p=0.0021).
- Total Motor Score (TMS): 59% slowing (2.01 vs 4.88; p=0.1741).
- Biomarkers: Cerebrospinal fluid (CSF) neurofilament light (NfL) levels decreased 8.2% from baseline at 36 months, suggesting reduced neuronal injury.
- Dose response observed:
The high-dose cohort showed consistent benefits across endpoints, whereas the low-dose group demonstrated variable trends, supporting a dose-dependent effect. - Safety profile: AMT-130 was generally well tolerated at both doses. No new drug-related serious adverse events were reported since 2022. Most adverse events were procedure-related and resolved.
Expert comments:1
“These groundbreaking data are the most convincing in the field to date and underscore potential disease-modifying effects in Huntington’s disease,” said Prof. Sarah Tabrizi, University College London Huntington’s Disease Centre.
“I believe AMT-130 has the potential to meaningfully slow disease progression – offering long-awaited hope to individuals and families impacted by this devastating condition.”
uniQure’s Chief Medical Officer, Dr. Walid Abi-Saab, called the findings “a fundamental shift,” adding:
“These results reinforce our conviction that AMT-130 can transform the treatment landscape for HD while providing important evidence supporting one-time, precision-delivered gene therapies for neurological disorders.”
Regulatory outlook1
- AMT-130 holds Breakthrough Therapy and Regenerative Medicine Advanced Therapy (RMAT) designations from the FDA.
- uniQure will meet with FDA regulators later this year and plans to submit a Biologics License Application (BLA) in Q1 2026.
- A United States (US) launch could follow later in 2026, pending approval.
Take-home messages for HCPs
- First therapy to show durable disease modification in HD: 75% slowing on cUHDRS at 36 months.
- Broad impact across endpoints: Motor, cognitive, and functional domains benefited.
- Safety manageable: Procedure-related adverse events (AE), no new drug-related serious AEs.
- Biomarkers support efficacy: CSF NfL chain reductions point to reduced neuronal injury.
- Regulatory path clear: BLA submission planned Q1 2026; US launch is proposed for later that year.
About Huntington’s Disease2,3,4
Huntington’s disease is a rare, inherited neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the HTT gene. This mutation produces a toxic huntingtin protein that drives progressive neuronal dysfunction and death, especially in the striatum and cortex. Although the function of this protein is unclear, it appears to play an important role in neurons in the brain.
- Epidemiology: HD affects an estimated 3–7 per 100,000 individuals of European ancestry, with onset typically between 30–50 years of age. The disorder appears to be less common in some other populations, including people of Japanese, Chinese, and African descent.
- Clinical course: The disease is characterized by a triad of motor, cognitive, and psychiatric symptoms, leading to progressive disability and dementia.
- Prognosis: Median survival is 15–20 years from symptom onset .
- Current management: No approved therapies alter disease progression. Existing care is symptomatic, including VMAT2 inhibitors for chorea and SSRIs for depression .
- Unmet need: Despite progress in genetic diagnosis and supportive care, there are no disease-modifying treatments.
References:
- uniqure. Press Releases. 2025. Available from: https://www.uniqure.com/investors-media/press-releases (accessed 25 September 2025).
- MedlinePlus. Huntington’s disease. 2025. Available from: https://medlineplus.gov/genetics/condition/huntingtons-disease/ (accessed 25 September 2025).
- Walker FO. Huntington’s disease. Lancet. 2007;369(9557):218-28. doi:10.1016/S0140-6736(07)60111-1
- Young AB. Huntingtin in health and disease. J Clin Invest. 2003;111(3):299-302. doi:10.1172/JCI17742
Editor: Katey Gabrysch, Editorial Director.
Disclosures: This short article was prepared by touchNEUROLOGY. The content was developed and edited by human editors. No fees or funding were associated with its publication. touchNEUROLOGY utilize AI as an editorial tool (ChatGPT (GPT-4o) [Large language model]. https://chat.openai.com/chat).
Cite: AMT-130 gene therapy achieves 75% slowing of Huntington’s disease progression. touchNEUROLOGY. 25 September 2025.
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