London — For the first time, an experimental treatment appears to slow the relentless march of Huntington’s disease, a fatal inherited disorder that corrodes the brain and upends entire families. In a pivotal Phase I/II program, patients who received a one-time gene therapy reported about 75 percent less disease progression at three years than a carefully matched comparison group, according to investigators and the therapy’s developer. The finding, still moving through the scientific publishing process, signals a striking shift in the prospects for people who until now have had only symptomatic drugs and the narrow comfort of monitoring a decline they could not halt.
The therapy, called AMT-130 and developed by UniQure, is delivered directly into the deep structures of the brain most damaged by Huntington’s disease. Surgeons use MRI guidance and a slow infusion to bathe target tissues in a viral vector that carries genetic instructions designed to quell production of the toxic mutant huntingtin protein. The procedure is long and technically demanding, typically lasting 12 to 20 hours, and it is intended to be given once. The newly disclosed three-year readout suggests that the investment of time, risk, and neurosurgical resources may be repaid with measurable preservation of function in movement, thinking, and day-to-day independence.
“We now have a treatment for one of the world’s more terrible diseases. This is absolutely huge. I’m really overjoyed,” said Prof. Sarah Tabrizi, the director of University College London’s Huntington’s disease centre, who led the trial. Her remarks captured the guarded optimism among clinicians who have watched decades of failure give way to a moment where the biology of Huntington’s may finally be yielding to intervention.
Huntington’s disease is caused by a single genetic error in the HTT gene that creates a malformed protein. That protein gradually poisons neurons, especially in the striatum, a hub of circuits that choreograph movement and behavior. The disease typically declares itself in midlife with mood changes, clumsiness, or subtle cognitive slips, then advances with choppy, involuntary movements, mounting disability, and early death. Because the mutation is autosomal dominant, each child of an affected parent carries a 50 percent risk of inheriting it. Many families have watched generation after generation receive the same verdict. The new data will not erase that genetic arithmetic, but it may finally change what a positive test can mean for the arc of a life.
What the three-year numbers show
The topline dataset covers 29 treated patients in the United States and United Kingdom who received either a lower or higher dose of AMT-130 and were followed for as long as 36 months. Investigators compared outcomes to a large, propensity-matched natural history cohort drawn from long-running observational studies of Huntington’s. The headline signal comes from the high-dose group at 36 months. On the composite Unified Huntington’s Disease Rating Scale, a standard measure that blends motor, cognitive, and functional items into a single score, patients on the higher dose declined about 75 percent more slowly than their matched peers. A key secondary measure of daily capability, Total Functional Capacity, also favored the therapy at three years. Biomarker data showed neurofilament light chain, a molecular signal of nerve injury, trending more favorably in treated patients than expected for this stage of illness.
Those clinical and biomarker signals align, at least directionally, with previous two-year updates that hinted at disease modification. The three-year readout adds durability and statistical weight. It also arrives with important caveats. The program uses an external control rather than an internal placebo arm for the long-term comparison. While the matching methods are considered robust, an externally derived counterfactual is never a perfect proxy. The sample size is modest, as is common in rare neurodegenerative conditions. The field is now watching for a full peer-reviewed report with methods, subgroup analyses, and adjudicated adverse events.
How the therapy works inside the brain
AMT-130 is built on an adeno-associated virus vector that acts like a shuttle. Surgeons thread micro-catheters to precise targets within the striatum, including the caudate and putamen. Over many hours, the vector infuses into the tissue. Once there, it delivers a sequence that guides cells to reduce production of the mutant huntingtin protein. The approach is highly localized. It does not circulate widely or require repeated dosing. That is a strength, because it focuses the effect where pathology is worst. It is also a constraint, because Huntington’s injures networks beyond the striatum, and no one yet knows the optimal anatomical footprint or depth of protein lowering needed for the best long-term outcome.
Neurosurgeons accustomed to functional procedures for Parkinson’s disease and epilepsy will recognize the precision and imaging support required for this therapy. Specialized cannulas, MRI guidance, and careful flow control are necessary to ensure that the gene vector spreads evenly without reflux along the catheter tract. The procedural learning curve and the limited number of centers with this expertise will shape how quickly the treatment can be adopted if it wins regulatory approval. In the United Kingdom, questions of capacity will intersect with NHS treatment realities around staffing and scanner time.
What it could mean for patients and families
The difference between a person who can still work, drive, and manage a household and a person who needs help dressing can be a few points on Huntington’s rating scales. A 75 percent slowing after three years, if confirmed and sustained, could translate into years of preserved independence for many patients. That is not a cure. It is not a reversal of established damage. But in a condition that for generations has offered only counseling, symptomatic drugs, and support groups, a credible slowing of decline changes medical decision-making and family planning in concrete ways.
The new data could also alter genetic testing behavior. Many at-risk adults have deferred or declined testing because knowledge of a positive result changed nothing medically and threatened work, insurance, and relationships. If an approved intervention allows treatment to start earlier in the disease course, more people may choose to learn their status while they still have time to intervene. Preparing that pathway will require counseling resources, insurer clarity, and expansion of specialist centers that can safely deliver gene therapy and manage long-term follow-up.
What comes next on regulation and timelines
UniQure says it plans to seek U.S. regulatory review, with a filing anticipated in early 2026. The company has discussed an accelerated pathway that reflects the severity of the condition and the absence of approved disease-modifying options. If a review is accepted and proceeds on standard timelines, a U.S. decision could arrive later that year. European and U.K. reviews would likely follow on their own calendars. The agency focus will extend beyond efficacy signals to the totality of safety data, procedural reliability across centers, and the feasibility of post-marketing commitments to track long-term outcomes.
The unresolved questions
Key uncertainties remain. The field needs full publication of the data, including how patient selection, surgical technique, and postoperative management influenced outcomes. Investigators will need to track whether slowing at three years holds at four and five years. The durability of protein lowering and the anatomical spread of vector expression will be crucial. Interaction with age, disease stage, and CAG repeat length could reveal subgroups who benefit more or less. Finally, the external control methodology, though strengthened by careful matching, will be scrutinized. Some experts will press for a larger confirmatory study with an internal control to lock down estimates of effect size before widespread adoption.
Safety, side effects, and the realities of brain surgery
Gene therapy in the brain is not risk free. Early program updates have noted hospitalizations following some high-dose procedures and transient elevations in biomarkers associated with neural stress. The latest disclosure characterizes safety as manageable, but the community will want specifics. The procedure requires general anesthesia, many hours in a scanner suite, and postoperative observation by teams with uncommon skills. Immunosuppression protocols may be considered for some patients to reduce inflammation. That means not every hospital can or should offer this therapy immediately, and not every patient will be an ideal candidate.
Cost, access, and the infrastructure challenge
Even before a price is set, the resources required imply that AMT-130 will be expensive, and not only in the list price. Comprehensive programs will need neurosurgeons trained in convection-enhanced delivery, interventional neuroradiologists, anesthesiologists familiar with prolonged MRI-guided procedures, movement disorder neurologists, and rehabilitation services. Payers will ask how to stage care, which centers qualify, how outcomes will be tracked, and how to mitigate the financial blow to families already stretched by caregiving. Those questions land amid higher-education and hospital budget pressures driven by policy uncertainty and headline-risk controversies, including the occasional research funding freeze that can chill clinical translation. Workforce and reimbursement rules also matter for tertiary centers that anchor neuroscience programs, as seen recently in debates touching hospitals and labs in the US.
How it compares with earlier disappointments and other approaches
For more than a decade, Huntington’s trials have tested ideas that looked strong in animals but faltered in people. Antisense oligonucleotides aiming to silence the mutant gene stumbled when dosing schedules, off-target effects, or insufficient lowering undercut clinical benefit. Small molecules that adjusted neurotransmission improved symptoms but never slowed the disease. The current signal does not invalidate those platforms. Instead, it suggests that deep, local, and durable lowering of mutant huntingtin can move the needle and that surgical gene delivery deserves continued testing alongside next-generation oligonucleotides and oral HTT-lowering agents. The neurodegenerative field will inevitably compare this landmark to hard-won gains in Alzheimer’s, including prevention-minded studies like the Roche Alzheimer’s prevention trial, while noting that Huntington’s genetics provide a clearer target and earlier foothold.
Voices from the Huntington’s community
Families have welcomed the news with a mix of joy and pragmatism. Many have carried parents through the disease and now look at their own futures with the same fear. Some are already asking how soon the therapy could be available, whether it can help those with advanced symptoms, and what the pathway would be for children who carry the mutation but have not yet developed signs. Clinicians are counseling patience and perspective. The best near-term candidates are likely to be people in early manifest stages who can tolerate surgery, have the anatomical targets intact on imaging, and can access specialist centers.
Why a cautious tone still matters
The scientific bar for declaring a disease-modifying effect in neurodegeneration is high. Three-year signals on validated scales are encouraging. They are not yet definitive proof of a long-term transformation. Huntington’s unfolds over decades. It reaches into cognition, behavior, and family life in ways that do not fit neatly into single endpoints. That is why independent replication, publication, and post-approval follow-up will be essential, even if the therapy clears regulatory hurdles. Clinicians also point to regulator-level standards and risk communication shaped by global bodies and national agencies, guidance that has framed debates from analgesic safety to pregnancy warnings and beyond. Readers can see this context in our reporting on WHO and MHRA guidance as a reminder that medical claims are ultimately tested against data, not headlines.
The bottom line
For the first time, a treatment appears to slow Huntington’s disease by a magnitude that matters to patients and caregivers. The signal comes from a demanding neurosurgical gene therapy with a plausible biological mechanism and a growing body of clinical and biomarker data. The path ahead runs through regulators and through hospitals capable of delivering a complex procedure safely and consistently. If those gates open, a diagnosis that has long felt like a one-way march may finally offer a different trajectory. That change would not only alter medical practice. It would rewrite the conversations families have around kitchen tables when they decide whether to get tested, when to tell their children, and how to plan for a future that might, at last, bend toward more time in control.
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