Huntington’s Disease (HD): A Rare and Deadly Disorder
uniQure is developing a gene therapy for Huntington’s disease (HD), a rare, fatal, neurodegenerative genetic disorder that affects motor function and leads to behavioral symptoms and cognitive decline in young adults, resulting in total physical and mental deterioration. HD is caused by the expansion of CAG trinucleotide in exon 1 of a multifunctional gene coding for protein called huntingtin.
Huntington’s disease affects approximately 75,000 people in the U.S., Europe and UK, making this one of the largest clinical unmet needs in the rare disease field. Despite the clear etiology of the disease, there are no therapies available to treat the disease, delay its onset, or slow the progression of a patient’s decline.
uniQure’s AMT-130 for Huntington’s Disease
Our investigational gene therapy candidate ifezuntirgene inilparvovec (AMT-130) consists of an AAV5 vector carrying an artificial micro-RNA specifically tailored to silence the huntingtin gene, leveraging our proprietary miQURE™ silencing technology. The therapeutic goal is to inhibit the production of the mutant protein (mHTT). Using AAV vectors to deliver micro-RNAs directly to the brain for non-selective knockdown of the huntingtin gene represents a highly innovative and promising approach to treating Huntington’s disease.
AMT-130 is the first investigational therapy for Huntington’s disease to have received Breakthrough Therapy and Regenerative Medicine Advanced Therapy (RMAT) designations from the FDA. Ifezuntirgene inilparvovec also holds Fast Track designation from the FDA.
AMT-130 administration animated video
Animated illustration of how AMT-130 is administered into the caudate and striatum regions of the brain via a micro-catheter
A Differentiated Gene Therapy Approach
uniQure’s gene therapy candidate for Huntington’s disease is differentiated in that:
AMT-130 is administered one time with potentially long-term effects.
AMT-130 is precision-delivered directly to diseased areas of the brain, minimizing systemic exposure.
AMT-130 suppresses both the huntingtin protein and the highly toxic exon‑1 isoform.
AMT-130 is administered via a standard stereotactic procedure that can be broadly performed.
Phase I/II Clinical Trial of AMT-130
uniQure is conducting two multi-center, dose-escalating, Phase I/II clinical studies to explore the safety, tolerability, and exploratory efficacy signals of AMT-130 for the treatment of Huntington’s disease.
In the U.S. study, a total of 26 patients with early manifest Huntington’s disease were randomized to treatment (n=6 low dose; n=10 high dose) or an imitation (sham) procedure (n=10). Treated patients received a single administration of AMT-130 through MRI-guided, convection-enhanced stereotactic neurosurgical delivery directly into the striatum (caudate and putamen). The study consists of a blinded 12-month core study period followed by unblinded long-term follow-up of treated patients for five years. An additional four control patients crossed over to treatment. The European open-label Phase 1b/2 study of AMT-130 enrolled 13 patients with early manifest Huntington’s disease (n=6 low dose; n=7 high dose).
A third cohort enrolled an additional 12 patients across sites in the U.S. and EU.This cohort was randomized to explore both doses of AMT-130 in combination with immunosuppression, using the current, established stereotactic administration procedure.
A fourth U.S.-based cohort is evaluating high-dose AMT-130 in up to 6 patients with lower striatal volumes compared to those of patients enrolled in previous cohorts.Additional details are available on www.clinicaltrials.gov (NCT04120493).
Advancing AMT-130 for the treatment of Huntington’s disease
In September 2025 we announced positive topline data from the pivotal Phase I/II study of AMT-130 for the treatment of Huntington’s disease.The study met its prespecified primary endpoint, with high-dose AMT-130 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. 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.
In September 2026 we announced the submission of a Biologics License Application (BLA) to the U.S. FDA for the accelerated approval of AMT-130. We also announced that a Marketing Authorisation Application (MAA) for AMT-130 has been submitted to the United Kingdom’s (U.K.) Medicines and Healthcare products Regulatory Agency (MHRA).
The BLA and MAA are supported by the previously announced three-year data analysis from the Phase I/II clinical study of AMT-130, compared to a propensity score-matched external control derived from the Enroll-HD natural history database.
In September 2026 we announced additional data from the ongoing Phase I/II studies of AMT-130 for the treatment of Huntington’s disease.
