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Huntington's disease is caused by an expanded stretch of the HTT gene, the gene that makes the huntingtin protein. The altered protein is cut into toxic fragments that build up in nerve cells in the brain, and those nerve cells stop working and eventually die^[12]. AMT-130 aims to lower how much huntingtin nerve cells in the striatum, the deep brain region made up of the caudate and putamen, make^[1].

It uses an AAV5 virus shell, emptied of its own genes, to carry instructions for a microRNA, a short strand of genetic material that silences a matching gene message^[11][1].

uniQure says the microRNA, built on its miQURE platform, is designed to silence the huntingtin gene and a shorter, potentially toxic piece of the protein called the exon 1 fragment^[1]. The US trial record calls it a total huntingtin gene lowering therapy^[11]. It is given once^[1].

The US Phase 1/2 study (NCT04120493) began on September 6, 2019 at 12 US sites and enrolls adults aged 25 to 65 with early Huntington's disease, 40 or more CAG repeats in the HTT gene and a Total Functional Capacity score of 9 to 13 in most cohorts^[11]. uniQure says the randomized part of the US study enrolled 26 people, including a group that had a sham procedure, in which surgeons make skin incisions but do not drill into the skull; a later cohort of 12 received either dose with immune-dampening medicines, and a fourth cohort of 6 is testing the high dose in people with smaller striatal volumes^[1][11]. A European open-label study (NCT05243017) enrolled 13 people, according to uniQure; ClinicalTrials.gov lists 14^[1][13].

On September 24, 2025 uniQure reported 36-month results for 12 people on the high dose, with data through June 30, 2025. Compared with a matched outside group of 940 people from the Enroll-HD natural history study, the cUHDRS, a combined score of movement, thinking and daily function, worsened 75% more slowly (a change of minus 0.38 against minus 1.52, p=0.003), and Total Functional Capacity worsened 60% more slowly (p=0.033). Neurofilament light, a marker of nerve damage in spinal fluid, was 8.2% below its starting level^[9].

On September 29, 2026 uniQure reported data through June 30, 2026 against an updated Enroll-HD comparison group. At 36 months, in 15 high-dose participants, cUHDRS worsened 80% more slowly and Total Functional Capacity 67% more slowly than in the outside group. At 48 months, in 12 high-dose participants, cUHDRS, the pre-specified main measure for that analysis, worsened 44% more slowly, a difference that was not statistically significant (p=0.144), and Total Functional Capacity worsened 61% more slowly.

Neurofilament light in spinal fluid was 6% below its starting level at 36 months in 14 participants and 4% above it at 48 months in 11 participants. uniQure said 53% of the comparison group's 48-month data were missing and argued that this likely understated the benefit. uniQure called the p-values for the 36-month and Total Functional Capacity results nominal^[3]. These comparisons are with people outside the trial, not with a placebo group.

uniQure said on November 2, 2026 that it and the FDA have aligned on key parts of a confirmatory trial: about 200 people randomized 2 to 1 to AMT-130 or standard care, with Total Functional Capacity at 36 months as the main measure, and that it plans to begin screening in the US by the end of 2026^[1]. That trial was not listed on ClinicalTrials.gov as of November 7, 2026.

AMT-130 has no FDA label, so its official side effects and warnings are not set. uniQure reported on September 29, 2026 that the therapy was generally well tolerated at both doses, that the most common side effects were related to the surgical procedure used to give it, and that all of these had resolved^[3].

In the same release uniQure said 5 high-dose participants had a serious side effect related to treatment involving inflammation of the brain and spinal cord, all of which fully resolved^[3]. uniQure also reported that 1 person in a low-dose group died by suicide about 5 years after treatment, a death the study investigator assessed as unrelated to treatment^[3]. uniQure's November 4, 2026 update described the safety profile as manageable across all 51 people treated so far^[2].

The US trial's main measure is safety, including MRI checks for swelling and inflammation in the brain^[11].

The US Phase 1/2 study began in September 2019 and the European study in October 2021^[11][13]. On June 2, 2025 uniQure said the FDA had agreed that the cUHDRS could serve as an intermediate measure for accelerated approval and that Enroll-HD may be acceptable as the outside comparison group^[10]. uniQure reported its 3-year results on September 24, 2025^[9].

After a pre-BLA meeting in October 2025, uniQure said the FDA no longer agreed that the Phase 1/2 data compared with an outside group could serve as the main evidence for an application, and that the timing of its filing was unclear; BioSpace reported the shift on November 3, 2025, and uniQure repeated it in its November 10, 2025 results^[8][7].

On March 2, 2026 uniQure said that, after a Type A meeting, the FDA could not agree that those data were enough and strongly recommended a randomized, double-blind, sham surgery-controlled study^[6]. uniQure then held a Type B meeting with the FDA in June 2026, and said on July 29, 2026 that the meeting minutes called an accelerated approval filing based on the existing data reasonable, while the FDA wanted to agree on the confirmatory study first^[5]. uniQure announced on September 2, 2026 that it had submitted the application to the FDA and to the UK's MHRA^[4], and the FDA accepted it for priority review on November 2, 2026^[1]. uniQure says the MHRA validated its UK application in the third quarter of 2026^[2].

AMT-130 holds the FDA's Breakthrough Therapy, RMAT and Fast Track designations^[1]. The FDA had not announced a decision or an advisory committee date as of November 7, 2026.