A global clinical trial evaluating the experimental gene therapy UCL has demonstrated a 75 percent reduction in disease progression over three years for patients receiving a high dose, according to trial sponsor uniQure and researchers at UCL. Announced by investigators, the findings mark the first time a drug trial has reported a continuing, statistically significant slowing of Huntington’s disease.
Gene Therapy Trial Shows Significant Slowing of Huntington’s Disease
Huntington’s disease is a fatal hereditary neurodegenerative disorder caused by a single genetic mutation in the HTT gene, which directs cells to produce a toxic version of the huntingtin protein. The condition typically strikes in mid-adulthood, leading to physical, cognitive, and behavioral decline, and is normally fatal within 20 years. Individuals with an affected parent carry a 50 percent chance of inheriting the mutation. Approximately 8,000 people live with Huntington’s disease in the UK, while the European Union, UK, and United States collectively account for about 75,000 cases, according to uniQure.
Trial Design and Biomarker Findings
The Phase I/II clinical trial involved 29 participants who completed up to 36 months of follow-up, with 12 patients receiving a high dose and providing a full 36 months of data. AMT-130 is administered via a single dose injected directly into the brain to reduce levels of toxic proteins. Researchers observed that spinal fluid levels of neurofilament light chain (NfL)—a biomarker of neuronal damage—were lower in treated patients compared to baseline measurements, contrasting with expected natural increases of 20 to 30 percent over three years.
Investigators stated that these biomarker patterns suggest the course of the disease has been modified and neuronal damage slowed. Furthermore, the therapy was found to be generally well-tolerated with a manageable safety profile.
Expert Reactions and Regulatory Outlook
Professor Sarah Tabrizi of the UCL Huntington’s Disease Research Centre, UCL Queen Square Institute of Neurology, and the UK Dementia Research Institute at UCL, who served as lead scientific advisor on the trial, described the results as world-changing. l am thrilled that this study of AMT-130 showed statistically significant effects on disease progression at 36 months,
Tabrizi said, noting that some trial patients have remained stable over time and that one medically retired patient was able to return to work.
Siddharthan Chandran, Director of the UK Dementia Research Institute, called the findings incredible news that offers real hope to affected families. However, independent experts noted that the results come from a press release and have not yet been peer-reviewed or published in a medical journal. Roger Barker, a professor of clinical neuroscience at the University of Cambridge, urged caution, pointing out that previous experimental therapies for Huntington’s have initially appeared promising before ultimately failing, and that larger studies will be required to confirm efficacy.
Next Steps for Approval
Following the trial results, uniQure plans to submit an application to the US Food and Drug Administration early next year requesting accelerated approval to market AMT-130. Subsequent applications are planned for the UK and Europe.
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