Gene Therapy Slows Huntington’s Disease Progression by 75% in Early Trial

A Huntington’s disease gene therapy showed a 75% slowing of disease progression over three years in a small, early-stage trial, researchers said. The study, conducted by Uniqure and collaborating investigators, enrolled 29 participants with Huntington’s disease who were assigned to one of two doses of an experimental therapy designed to silence the mutated huntingtin gene. The findings have not yet been published in a peer‑reviewed scientific journal.

The therapy uses a DNA sequence carried by an inactivated virus vector to instruct brain cells to reduce huntingtin protein production. The operation involved drilling through the skull to reach the striatum, a brain region most affected by the disease, and delivering the gene therapy through a single surgical procedure lasting 12 to 15 hours. Of the 29 participants, 17 received the higher dose and showed a 75% slowing in overall progression; 12 received the lower dose, which was one-tenth as concentrated, and showed progression similar to untreated patients, though some symptoms improved. Researchers compared treated participants with about 2,000 untreated Huntington’s patients matched by age and disease stage, the only comparator available given no approved disease-modifying therapies.

Biomarker data described in the study include levels of neurofilament, a protein released by damaged nerve cells. In Huntington’s, neurofilament typically rises in the early years of the disease, signaling neuronal injury. Among those who received the gene therapy, neurofilament levels fell from baseline or remained near baseline, a pattern researchers say suggests neurons were being saved and the disease’s trajectory could be altered at least for a period of time. The team stressed that biomarker changes do not alone prove clinical benefit, but they are consistent with the slowed clinical progression observed in the high-dose group.

The high-dose group’s 75% slowing refers to broader disease progression across several functional measures, including motor, cognitive, and daily-living tasks. The study’s investigators emphasized that while the result is striking, it derives from a relatively small number of participants and is not yet validated in a peer‑reviewed publication or in a broader population. The 17 participants who received the high dose and the 12 who received the lower dose were followed for multiple years and compared against a historical cohort of untreated Huntington’s patients matched to age and disease stage. The comparison to untreated individuals reflects the lack of approved disease-modifying therapies for Huntington’s and the ethical and logistical challenges of designing a traditional placebo-controlled surgical trial for a brain intervention.

Researchers highlighted that the drug-delivery approach required invasive brain surgery. The striatum, a cradle of movement control and certain cognitive processes, is among the earliest regions to degenerate in Huntington’s disease. By delivering the therapy directly to this region, investigators aimed to suppress the production of the huntingtin protein before it forms toxic aggregates that disrupt neuronal function. Although the lower-dose group did not show a meaningful difference from placebo on most clinical measures, some participants in that cohort did experience symptom improvements, underscoring the potential for dose optimization and individualized treatment planning in future studies.

Dr. Sarah Tabrizi, director of the University College London Huntington’s Disease Centre and a lead investigator on the study, said the results are encouraging for a field that has long sought a disease-modifying option. She noted that neurofilament data aligned with the clinical findings and suggested neuron preservation in patients who received the therapy. Tabrizi also indicated that the results have shifted her thinking toward testing the therapy earlier in the disease course, including patients who are presymptomatic but carry the Huntington’s gene, with the aim of delaying or preventing symptom onset.

“Given what we are seeing, there is a real possibility that extending benefits to people even earlier in the disease could delay, or in the best case, prevent many of the worst symptoms from ever appearing,” she said. In discussing the potential to reach people at earlier stages, she suggested that a future research emphasis could focus on Stage 0 or Stage I carriers who have not yet developed clinical symptoms, to explore whether therapy could avert disease onset altogether.

Walid Abi‑Saab, Uniqure’s chief medical officer, acknowledged the practical challenges of the approach. He explained that because the brain surgery is invasive and carries risks, the researchers could not reasonably subject half of the participants to a sham surgery to serve as a control. Instead, the team relied on rigorous long-term follow-up and careful matching to historical untreated patients to assess therapeutic impact while maintaining patient safety. Abi‑Saab stressed that the study’s design sought to provide meaningful evidence of effect without exposing participants to unnecessary risk.

Matt Kapusta, CEO of Uniqure, called the therapy transformational and framed the path forward in regulatory terms. The company plans to file for accelerated FDA approval to treat Huntington’s in the first part of the coming year. If the FDA grants accelerated approval, Uniqure said it would be prepared to provide the therapy to patients later in 2026, pending final safety data and manufacturing considerations. Kapusta emphasized the potential for the treatment to buy time for patients and families, delivering longer periods of functionality and life with loved ones, even if the approach ultimately requires refinement and broader validation.

The Huntington’s community currently has no approved disease-modifying therapies, and treatments focus on managing symptoms and supporting daily functioning. Researchers caution that the current findings, while promising, must be replicated in larger studies and subjected to peer review before the therapy can be widely recommended. The invasiveness of the surgical delivery will remain a central consideration in evaluating broader use, cost, and long-term safety. Independent replication, longer follow-up, and additional trials involving diverse patient populations will be necessary to determine whether the observed 75% slowing represents a durable, generalizable effect.

In the immediate term, the study underscores the growing interest in gene-therapy strategies that target the root genetic driver of neurodegenerative diseases. Scientists are investigating various approaches to reduce or silence disease-causing genes, and this Huntington’s trial marks one of the most advanced demonstrations to date that a gene-targeted therapy can meaningfully alter disease progression in humans. If validated, the approach could pave the way for similar interventions in other neurological disorders where a single dominant gene drives pathology. The field awaits peer-reviewed publication, additional trials, and careful assessment of risk–benefit profiles as researchers, clinicians, regulators, and patient advocates weigh how best to translate these early signals into durable, safe, and accessible therapies.