A new gene therapy treatment, AMT-130, appears to slow disease progression in Huntington’s disease (HD), according to results from a phase I/II trial led by researchers at University College London (UCL) and Amsterdam-based biopharma company uniQure.
In the study, 29 patients received AMT-130, with 12 receiving a high dose and completing 36 months of follow-up. Their outcomes were compared to a matched external “natural history” cohort from the Enroll-HD study, which tracks the usual course of HD in untreated patients. At the 36-month mark, those treated with the high dose of AMT-130 showed about 75 percent less disease progression (as measured by a composite of motor, cognitive, and functional scales) than the comparison group. There were also statistically significant improvements in other key assessments, including Total Functional Capacity and various motor and cognitive metrics.
AMT-130 works by delivering engineered DNA via a harmless viral vector directly into the striatum (a brain region heavily affected in HD), using neurosurgical stereotactic techniques guided by MRI. The DNA instructs cells to make an RNA that binds to and degrades the messenger RNA for mutant huntingtin, a protein encoded by the HTT gene that affects development in the brain and other tissues, thereby reducing production of the disease-causing protein. A single dose is intended to last a lifetime.
Upon hearing the news, Roger Barker, Professor of Clinical Neuroscience and Honorary Consultant Neurologist, University of Cambridge, said, “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. The data as reported shows improvements across a number of measures including a proxy marker of nerve cell loss called neurofilament light.
“Whether injections restricted to specific brain sites can slow down the disease across the whole brain is still unclear but the data from this trial is much better than anything we have seen before, so this looks good but currently does depend on brain surgery for delivery, which is not without risk. The results are encouraging but it is early days and we have been here before with other similar therapies for Huntington’s disease.”
Neil Ward, VP EMEA, PacBio, said, “Until now there has been no viable treatment for Huntington's, which meant many at-risk individuals weren’t offered testing or chose not to pursue it, even with a family history of the disease. This breakthrough could change that by giving people a reason to seek testing and even inform family planning. It also shows what could soon be possible for other devastating genetic disorders.”
Huntington’s belongs to a broader category of repeat expansion disorders, which arise when sections of DNA are repeated in ways that interfere with normal gene function. Although Huntington’s has been comparatively easier to investigate, many related conditions have remained difficult to study or diagnose. The challenge stems from the fact that older genomic tools could not handle very long or complex repeat sequences, and testing often requires multiple separate analyses, an impractical approach for national health systems.
Ward added, “Advances in sequencing technology now make it possible to study and diagnose these conditions in a single test, opening the door to more timely diagnoses and, ultimately, new therapies that could change lives across many families.”
UCL and UniQure investigators describe the result as “groundbreaking”, with plans to file for accelerated approval expected early next year.
UniQure CMO Walid Abi-Saab said, “These findings reinforce our conviction that AMT-130 has the potential to fundamentally transform the treatment landscape for Huntington’s disease, while also providing important evidence supporting one-time, precision-delivered gene therapies for the treatment of neurological disorders … We are eager to discuss the data with the FDA at our pre-BLA meeting expected later this year, with the goal of submitting a BLA in the first quarter of 2026.”
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