On the 24th of September 2025 a major breakthrough for Huntington’s disease was announced by a research team at UCL: a new gene therapy delivered directly to the brain that slowed disease progression by a reported 75%. But what does this mean for clinicians and patients? And what are the challenges for bringing promising results into practice?

Prof Roger Barker, Professor of Clinical Neuroscience and Honorary Consultant Neurologist, University of Cambridge, commended the data and the results, but advised a balanced perspective.

“The results are encouraging but it is early days and we have been here before with other similar therapies for Huntington’s disease,” he said referring to the 2017 news of a gene therapy for Huntington’s disease delivered into the spinal fluid: BBC World Service – Health Check, ‘Breakthrough’ in Treating Fatal Brain Condition

He continued: “The trial involves injecting the therapy directly into the brain using a special technique into the striatum on each side of the brain- so its widespread adoption across neurological centres will not be straightforward if it is shown to truly work. The striatum is the area that has the greatest pathology in HD, which is why it was targeted in this trial and is known to mediate many but not all the features of HD and the data as reported shows improvements across a number of measures including a proxy marker of nerve cell loss called neurofilament light.”

Prof David Rubinsztein, Professor of Molecular Neurogenetics and Deputy Director, Cambridge Institute for Medical Research, provided careful breakdown of the study approach, whilst recognising that the results are exciting:

“This is very promising news. Huntington’s disease is caused by a mutation that makes the huntingtin protein toxic to cells. Hence, reducing the levels of mutant huntingtin is a rational therapeutic strategy. uniQure have developed a way to accomplish this using a virus expresses an artificial microRNA that lowers huntingtin expression. The virus is administered into the brain.”

“The early stage trial that they have reported involves a modest number of patients and much of the control data were not from placebo-controlled patients but from existing natural history data of Huntington’s disease patients.  The results that were reported are from the high-dose group which comprised 17 patients, 12 who were followed up for 36 months. No data were reported from the low-dose group but the impression from the press release was that no significant benefits were seen with the low dose (which is fine if the high dose works and is well-tolerated).” 

“The analyses that have been reported are exciting as they suggest a clear slowing of disease progression measured with a range of tools along with a suggestion amelioration of neurodegeneration. While these headline results are from a press release and not from a publication where all the data and analyses can be seen, this provides real hope for this devastating disease. Importantly, this treatment strategy was generally well tolerated.  This approach, if successfully validated has much broader implications as it may have potential to reducing the levels of other toxic proteins causing other dementias, forms of Parkinson’s disease and forms of motor neuron disease.  This could be a major breakthrough.”

See all reactions in Science Media Centre here:

https://www.sciencemediacentre.org/expert-reaction-to-announcement-by-uniqure-of-topline-results-from-a-phase-i-ii-study-of-a-gene-therapy-to-slow-huntingtons-disease-progression/

Read the BBC article about the UCL Huntington's trial here: https://www.bbc.co.uk/news/articles/cevz13xkxpro