Understanding the 3-Year Findings Behind AMT-130 in Huntington Disease: Victor Sung, MD

WATCH TIME: 3 minutes

“The longer these patients remain relatively stable while untreated Huntington disease patients continue to progress, the wider that separation becomes. That’s what makes these three-year results so encouraging.”

Huntington disease (HD) is a progressive, inherited neurodegenerative disorder characterized by worsening motor dysfunction, cognitive decline, and psychiatric symptoms driven by mutant huntingtin protein accumulation. Despite advances in symptomatic management, there are currently no approved therapies capable of definitively slowing disease progression, making disease-modifying strategies a major focus of ongoing research.

AMT-130 (uniQure) is an investigational one-time gene therapy designed to reduce mutant huntingtin (HTT) mRNA and lower production of the toxic huntingtin protein. The therapy uses an adeno-associated virus serotype 5 (AAV5) vector to deliver a huntingtin-targeting microRNA directly into the caudate and putamen through MRI-guided stereotactic neurosurgical infusion. Early clinical development has focused on evaluating both long-term safety and the potential for sustained disease modification following a single administration.

At the 2026 American Academy of Neurology (AAN) Annual Meeting in Chicago, investigators presented 3-year follow-up data from the phase 1/2 AMT-130 program (NCT04120493). In the high-dose cohort, treated participants demonstrated a 75% slowing of disease progression on the composite Unified Huntington’s Disease Rating Scale (cUHDRS) compared with matched external controls, alongside favorable trends across motor, cognitive, and functional measures. Investigators also reported reductions in cerebrospinal fluid neurofilament light chain (NfL), a biomarker of neurodegeneration, while no new long-term safety concerns emerged during follow-up.

During the meeting, study author Victor Sung, MD, professor of neurology and director of the Division of Movement Disorders at the University of Alabama at Birmingham, spoke with NeurologyLive^® about the implications of the findings. In the discussion, Sung explained the rationale and delivery approach behind AMT-130, reviewed the key clinical and biomarker outcomes observed through 3 years, and discussed what these early signals may mean for the future development of disease-modifying therapies in Huntington disease.

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