Huntington Disease Progression Significantly Slowed with Investigational Gene Therapy

AMT-130 (uniQure, Amsterdam, The Netherlands), an investigational gene therapy, was shown to substantially slow disease progression in people with Huntington disease (HD), according to topline results from a phase 1/2 clinical trial program (NCT05243017, NCT04120493). Participants in the program who received high-dose AMT-130 treatment showed benefits across functional, motor, and cognitive outcomes, supporting the potential for disease modification in HD, a condition with few therapeutic options available. AMT-130 uses an adeno-associated virus to carry a microRNA that targets and silences the huntingtin gene, lowering huntingtin protein levels.

The reported data draws from an analysis of 29 participants with HD. These individuals were randomized to receive either high-dose (n=17) or low-dose (n=12) AMT-130. Outcomes at 36 months were compared against external controls drawn from the Enroll-HD natural history dataset (high dose, n=940; low dose, n=626). Participants received a single, MRI-guided, stereotactic infusion of AMT-130 and were assessed for changes in clinical function and biomarkers of HD.

Compared with controls, at 36 months, participants treated with high-dose AMT-130 showed slowed disease progression according to the following measures:

• Composite Unified Huntington’s Disease Rating Scale (cUHDRS): 75% slowing in disease progression (P=.003).
• Total Functional Capacity (TFC): 60% slowing (P=.033).
• Symbol Digit Modalities Test (SDMT): 88% slowing (P=.057).
• Stroop Word Reading Test (SWRT): 113% slowing (P=.002).
• Total Motor Score (TMS): 59% slowing (P=.174)

Additionally, participants treated with high-dose AMT-130 showed a mean reduction of 8.2% in cerebrospinal fluid (CSF) neurofilament light chain (NfL) compared with controls.

“I believe these groundbreaking data are the most convincing in the field to date and underscore potential disease-modifying effects in Huntington’s disease, where an urgent need persists,” said Sarah Tabrizi, MD, FRCP, FRS, FMedSci, PhD, Professor of Clinical Neurology, Joint Head of the Department of Neurodegenerative disease, and Director of the University College London (UCL) Huntington’s Disease Center. “These data indicate that AMT-130 has the potential to meaningfully slow disease progression – offering long-awaited hope to individuals and families impacted by this devastating disease.”

According to a statement from uniQure, AMT-130 has received Food and Drug Administration (FDA) Breakthrough Therapy designation in April 2025 and Regenerative Medicine Advanced Therapy (RMAT) designation in June 2024. The company is planning on submitting a Biologics License Application for AMT-130 in 2026.  

Source: uniQure. uniQure announces positive topline results from pivotal phase I/II study of AMT-130 in patients with Huntington’s disease. uniqure.gcs-web.com. Published September 24, 2025. Accessed September 30, 2025. https://uniqure.gcs-web.com/news-releases/news-release-details/uniqure-announces-positive-topline-results-pivotal-phase-iii