Huntington’s disease (HD) has long been considered inexorable. It is a genetic brain disorder in which a faulty copy of the huntingtin gene causes a harmful protein to build up, gradually destroying nerve cells. Until now, treatments could ease symptoms but could not slow or reverse the underlying damage. That may change. Scientists and clinicians from University College London and gene therapy company uniQure have announced that a one-time therapy called AMT-130 appears to slow the progression of HD in people, a milestone never before reached in human trials.
How the treatment works
AMT-130 is a gene therapy delivered directly into the brain. In a delicate neurosurgical procedure, a harmless viral vector is injected into the striatum, a part of the brain especially affected in HD. That vector carries genetic instructions to produce a microRNA molecule designed to bind to the messenger RNA of the huntingtin gene. Once bound, that message is removed, reducing the production of both mutant and normal huntingtin proteins. Because the change is permanent in the treated brain cells, a single dose may last for life.
Other therapeutic approaches lower hunting via injections or pills, but they require repeated dosing and may not reach all regions of the brain. AMT-130 seeks a one-and-done effect inside the brain itself.
What the trial showed
In the Phase I/II trial, 29 patients were treated, 17 with a high dose of AMT-130 and 12 with a lower dose. Over 36 months of follow-up, 12 participants from each dose group reached the full three years of observation. Their clinical outcomes were compared not to placebo patients in the trial, but to a well-matched external control group drawn from the natural history registry Enroll-HD.
The results were striking. In those receiving the high dose, disease progression measured by the composite Unified Huntington’s Disease Rating Scale (cUHDRS) was slowed by 75 percent compared to matched controls. In numbers, treated patients’ average decline was — 0.38 on cUHDRS, vs — 1.52 in controls. That effect was statistically significant (p = 0.003).
The therapy also performed well on secondary outcomes. The Total Functional Capacity (TFC) measure, which reflects daily living ability, showed about 60 percent slower decline in treated patients. Cognitive tests (like processing speed and reading) showed large reductions in decline (e.g. ~88 % for one test), though some missed the threshold for statistical significance. Motor scores (movement symptoms) tended toward slowing, though these were not all statistically robust.
A biomarker known as neurofilament light (NfL), which reflects nerve damage, also moved in a favorable direction: NfL levels were modestly lower than baseline at 36 months in treated patients, whereas rising levels would have been expected. That suggests neurodegeneration may be reduced.
The safety profile appeared acceptable. Most side effects related to surgery, and no new serious drug-related adverse events have been reported since late 2022. The treatment was described as “well tolerated” across both dose groups.
Why this matters
Until now, no treatment has reliably changed the course of Huntington’s disease in humans. AMT-130 is the first to show a disease-modifying effect in a clinical trial. That means it may slow the damage rather than just manage symptoms.
Experts are cautiously optimistic. Professor Sarah Tabrizi of UCL, a lead advisor, said, “I am thrilled that this pivotal study of AMT-130 showed statistically significant effects on disease progression at 36 months … These groundbreaking data are the most convincing evidence in the field to date.” Professor Ed Wild, also on the trial, said his patients remained “stable over time in a way I’m not used to seeing” and noted that one patient who retired before the trial has even returned to work.
If confirmed in larger studies, AMT-130 could become the first approved therapy for HD transforming not only care but hope for families whose lives are shadowed by this condition.
Risks, limits and what remains unknown
This achievement is monumental but it is also early, and many questions remain. First, the trial compared treated patients with matched external controls, not an internal placebo group; that method is acceptable in rare disease trials but carries risk of bias.
Second, follow-up is currently just three years. We do not yet know whether benefits persist over longer time, or whether late side effects could emerge.
Third, the delivery method of brain surgery is complex and carries its own risks. Not every patient or center may be able to access such a procedure. As usage scales, surgical risk, logistical capacity, and cost will become important hurdles.
Fourth, we do not yet know whether earlier intervention (before symptoms) or different disease stages might yield better benefit. Researchers also need to learn the optimal dose, which brain regions to target, and whether combining therapies might improve outcomes.
Finally, cost will almost certainly be high, as is the case with many gene therapies. Ensuring fair access across countries and healthcare systems will require planning.
The path to approval and what lies ahead
UniQure plans to submit its data to the U.S. Food and Drug Administration in early 2026, seeking accelerated approval, and to engage European regulators such as the EMA. The company already holds Breakthrough Therapy and Regenerative Medicine Advanced Therapy (RMAT) designations, which should help streamline review.
Meanwhile, additional patients are being enrolled in expanded cohorts to strengthen safety and efficacy data. As more data accrue, the treatment may be tested in different disease stages or compared against other huntingtin-lowering therapies.
Scaling up manufacturing and building surgical networks in hospitals will also be critical to ensure that eligible patients can access the therapy.
What patients and families should understand today
If you or someone you know has Huntington’s disease, this result brings real cause for hope but it is not yet a cure, and it will take time before therapies based on it are widely available. Ask your neurologist or specialist center about ongoing trials and eligibility. Watch for announcements from HD patient advocacy groups and clinical centers about next steps in research and access.
While the excitement is justifiable, it should be tempered with realism: regulatory review, longer safety follow-up, manufacturing scale-up, and equitable access are all hurdles ahead. Still, for the first time in decades, science has delivered news that may truly alter the destiny of Huntington’s disease.
