Revolutionary Gene Therapy Slows Huntington's Disease for First Time

Historic Medical Breakthrough

For the first time in medical history, researchers have demonstrated that a treatment can meaningfully slow the progression of Huntington's disease. On a video call in early September, Sarah Tabrizi first saw the data that she and other researchers studying Huntington's disease had been chasing for decades: compelling evidence that a gene-targeting therapy could slow the relentless progression of the neurodegenerative brain disorder. This is the first time any drug has been shown to alter the course of HD in people in a clinical trial.

Sarah Tabrizi is part of Nature's 10, a list of people who shaped science in 2025. As director of the Huntington's Disease Centre at University College London, Tabrizi led the scientific advisory role for the groundbreaking AMT-130 gene therapy trial. Before these results, "I was beginning to get a little bit worried that maybe, by the time people develop symptoms, that it was going to be too late to treat", says Tabrizi, a neurologist who directs the Huntington's Disease Centre at University College London. But here was powerful validation that the window for treating the rare, hereditary condition remains open — offering a chance for meaningful, disease-modifying interventions.

Remarkable Trial Results

High-dose participants showed substantial slowing of decline across multiple measures, including 75% slower progression on the composite HD scale (cUHDRS), ~60% slowing in the decline of daily function, and favorable biomarker changes (notably reduced neurofilament light). In a three-year analysis of the study, Huntington's patients treated with a high dose of Uniqure's gene therapy, called AMT-130, lost an average of 0.38 points on a measure of disease progression called cUHDRS. That compared to a loss of 1.52 points for matched participants in an external control group based on a large, natural history study. The AMT-130 benefit was statistically significant and achieved the primary goal of the study.

For the first time in a study of this kind, the published results suggest that in a group of patients receiving the highest dose, disease progression stabilized. On average, patients did not worsen in their motor and cognitive abilities, something usually inevitable in Huntington's disease. The therapy requires complex brain surgery but was generally well-tolerated, with no new serious adverse events reported since December 2022.

Revolutionary Treatment Approach

AMT-130 is a gene therapy that permanently introduces new functional DNA into a person's cells. It consists of particles of a harmless, empty virus, plus a set of instructions encoded in custom-made DNA. The virus is injected directly into a part of the brain called the striatum which is particularly vulnerable in Huntington's disease. This is done using a highly complex neurosurgical technique called stereotactic surgery, in which tiny tubes called catheters are guided to the right part of the brain, supported by live MRI images.

Once in the brain, the virus particles enter the neurons and release the DNA cargo. The AMT-130 DNA becomes a permanent addition to the neuron. It contains a set of instructions for making a molecule of RNA which has been designed to bind to the RNA that is produced when a cell is making the huntingtin protein. When AMT-130 RNA binds to the cell's own huntingtin RNA, it summons an enzyme to destroy it.

Hope for Families Worldwide

Huntington disease, which affects 30,000 people in the United States and many more globally, results from a mutation in a gene called HTT, which encodes a protein called huntingtin that's key to neuron health. Professor Ed Wild, principal investigator of the UCL Huntington's Disease Centre trial site at UCL and UCLH, said: "This result changes everything. On the basis of these results it seems likely AMT-130 will be the first licensed treatment to slow Huntington's disease, which is truly world-changing stuff.

For people living with Huntington's, an effective, one-time therapy that significantly slows the loss of muscle control and cognition around mid-life could preserve years of quality relationships and gainful employment that would normally be lost to the disease. uniQure plans to discuss the data with the FDA later this year at a pre-Biologics License Application meeting, aiming to submit the application in early 2026. This breakthrough validates decades of research and offers unprecedented hope for families affected by this devastating genetic disorder.