Gene therapy is emerging as a potent approach for complex diseases that do not respond to conventional treatments, and scientists have now achieved a groundbreaking success in genetically modifying to decelerate Huntington’s disease.

According to a study from Uniqure, the developer of this experimental gene therapy, researchers observed a 75% deceleration in Huntington’s disease progression over a three-year period. This research has not yet appeared in a peer-reviewed scientific publication.

“I entered the trial with cautious optimism but considerable anxiety, as is typical when embarking on a gene-therapy study,” stated Dr. Sarah Tabrizi, director of the University College London Huntington’s Disease Center and a principal investigator for the study. She added, “I was astonished upon reviewing all the data; it was exceptionally clear that the gene therapy was effective.”

The research included 29 Huntington’s disease patients, each receiving one of two gene therapy dosages designed to target the huntingtin gene, which is mutated in this condition. This altered gene produces an abnormal huntingtin protein that forms toxic clumps, hindering normal nerve function. Over time, nerve cells—especially those in brain regions governing movement and cognitive abilities such as motivation, habit formation, and decision-making—deteriorate, resulting in both physical and cognitive manifestations.

All participants in the trial underwent monitoring for various biological and behavioral indicators, such as markers for degenerated nerve proteins in spinal fluid and their capacity to conduct daily routines, handle finances, and maintain employment. The gene therapy necessitated a 12- to 15-hour brain surgery where surgeons perforated the skull to reach the striatum, a deep brain region profoundly impacted by the impaired huntingtin protein. The surgeons administered the gene therapy, comprising DNA delivered via an inactivated viral vector, which contained instructions to inhibit the production of the huntingtin protein.

Among the 17 individuals administered the high dose, an overall 75% reduction in symptom progression was observed. The 12 participants receiving the lower dose—a tenfold less concentrated amount—exhibited progression comparable to a placebo group, though some reported symptom amelioration.

Dr. Walid Abi-Saab, Uniqure’s chief medical officer, explained that due to the invasive and hazardous nature of the brain surgery, researchers needed to devise a dependable method to assess the gene therapy’s impact without performing a sham surgery on some patients. Those who received the gene therapy were monitored over several years and contrasted with a cohort of approximately 2,000 untreated Huntington’s patients—given the current lack of disease treatments—who were carefully matched to the gene therapy recipients based on factors such as age and disease stage.

Tabrizi, who has dedicated two decades to researching potential Huntington’s therapies, characterized the 75% deceleration in disease progression among gene therapy recipients as “enormous.” She stated, “I have never witnessed anything demonstrating such a benefit.” Tabrizi noted that in Huntington’s patients, neurofilament levels—a product of damaged nerve cells—in spinal fluid typically rise by 30% to 45% during the initial stages of the disease. However, individuals in the study receiving gene therapy displayed a decrease in these levels, sometimes falling below their baseline. “This indicates that neurons are being preserved,” she affirmed.

She conveyed that these promising outcomes motivate her to consider applying the therapy to individuals at even earlier disease stages, envisioning the possibility of averting the emergence of many of the disease’s most severe symptoms. The trial participants were in Stage II or III, yet she believes, “When individuals carrying the Huntington’s gene are entirely healthy, we might be able to stop the disease from ever manifesting and prevent symptoms from ever appearing.” She concluded, “I personally wish to begin exploring how we can provide this therapy to people at Stage 0 or I to prevent this disease altogether.”

Matt Kapusta, Uniqure’s CEO, described the therapy as “transformative” and emphasized that providing patients with additional time with family, coupled with attenuated or reduced symptoms, is “invaluable.” Uniqure intends to petition the U.S. Food and Drug Administration for accelerated approval of the gene therapy for Huntington’s early next year, and should it be granted, they are ready to make it available to patients in late 2026.