Introduction to Huntington’s Disease and Gene Therapy
Huntington’s disease is a rare yet devastating neurodegenerative disorder affecting around 75,000 individuals across the US, EU, and UK. Characterized by progressive physical and mental decline, it stems from a mutation in the huntingtin gene, which leads to the accumulation of toxic proteins in the brain. Currently, there are no approved therapies aimed at slowing the onset or progression of Huntington’s disease, making any advancements in treatment critically important.
Pivotal Study Results for AMT-130
Recently, uniQure N.V. (MA, USA) published positive results from its Phase I/II clinical study of AMT-130, a groundbreaking gene therapy targeting Huntington’s disease. The study involved two multi-center, dose-escalating trials assessing the safety, tolerability, and efficacy of AMT-130. Encouragingly, the trial met its primary endpoint, demonstrating that patients who received the higher dose of AMT-130 experienced a significant 75% slowdown in disease progression over 36 months, compared to untreated controls.
Study Design and Patient Outcomes
The study included 29 participants, with 17 receiving a high dose and 12 a low dose of AMT-130. After 36 months, evaluations showed that patients on the higher dose demonstrated minimal decline in their condition, measured by a standard Huntington’s disease rating scale. Additionally, successful results were observed on key secondary endpoints, with a 60% reduction in the decline of patients’ ability to function independently.
Cognitive and Motor Improvements
Patients treated with AMT-130 also showed significant improvements in cognitive and motor functions. Tests measuring thinking speed, reading ability, and motor control indicated enhanced performance in treated patients. More notably, the therapy impacted a critical biomarker for neurodegeneration. Participants exhibited an average decrease in cerebrospinal neurofilament light protein (CSF NfL) levels by -8.2%. Elevated levels of CSF NfL are closely linked to the severity of Huntington’s disease symptoms, making these findings particularly promising.
Tolerability and Side Effects
Throughout the trial, AMT-130 was deemed generally well-tolerated at both dose levels. As of June 30, 2025, no new serious drug-related adverse events have been reported since December 2022, which adds to the therapy’s safety profile.
Looking Ahead: Regulatory Progress and Future Implications
uniQure’s CEO, Walid Abi-Saab, expressed enthusiasm about the trial results, emphasizing the potential for AMT-130 to change the treatment landscape for Huntington’s disease. Given the promising data, the gene therapy has received Breakthrough Therapy and Regenerative Medicine Advanced Therapy designations from the FDA, indicating its potential to fulfill unmet medical needs.
Next Steps for uniQure
With plans to engage in discussions with the FDA later this year, uniQure aims to file their Biologics License Application in early 2026. This proactive step underscores the commitment to making AMT-130 a viable treatment option for those suffering from Huntington’s disease.
Conclusion
The results from the AMT-130 study represent a beacon of hope for Huntington’s disease patients and their families. As research continues to advance, gene therapy could pave the way for innovative solutions to combat this challenging disorder, potentially altering the course of neurodegenerative diseases as a whole.
