Huntington’s disease (HD), a devastating inherited neurodegenerative disorder, has long been considered incurable, with treatments only managing symptoms rather than altering its relentless progression. However, in 2025, a groundbreaking gene therapy called AMT-130 has emerged as the first treatment to show statistically significant slowing of disease progression in clinical trials, marking a historic milestone in HD research[1][2][3].
Huntington’s disease is caused by a mutation in the huntingtin gene, leading to the production of a toxic huntingtin protein that damages brain cells, particularly in regions controlling movement, cognition, and behavior. Symptoms typically begin in mid-adulthood and progressively worsen over 10 to 30 years, ultimately leading to death. Until now, no therapy has been able to modify the disease course itself[1][4].
The new treatment, AMT-130, is a one-time gene therapy that involves a surgical procedure guided by magnetic resonance imaging (MRI). During this procedure, surgeons infuse an engineered virus carrying a microRNA directly into the caudate and putamen—brain regions severely affected by HD. This microRNA targets the messenger RNA responsible for producing the toxic huntingtin protein, effectively reducing its production without altering the DNA itself. This approach offers a key safety advantage over other genetic therapies that modify DNA directly[1][3][4].
In a small clinical trial involving 29 participants in the early stages of HD, those receiving a high dose of AMT-130 experienced a remarkable slowing of disease progression by approximately 75% over three years compared to a matched external control group. This slowing was observed across multiple clinical measures, including motor function, cognitive abilities, and daily living activities. Additionally, researchers detected a reduction in the levels of the toxic huntingtin protein in the spinal fluid of treated patients, indicating a biological effect consistent with the therapy’s mechanism[1][2][3][4].
Despite these promising results, experts urge caution. The trial was small, with fewer than 30 participants, and comparisons were made against an external control group rather than a placebo-controlled group within the same trial. This limits the strength of the conclusions and means further studies with larger participant numbers and longer follow-up are necessary to confirm the therapy’s efficacy and safety. Moreover, the treatment requires invasive brain surgery, which carries inherent risks and may not be suitable for all patients[2][3][4][5].
The significance of AMT-130 lies in its potential to be the first FDA-approved disease-modifying therapy for Huntington’s disease. If approved, it could transform the outlook for patients by extending the period of independence and slowing the devastating decline caused by HD. However, it is important to emphasize that this therapy is not a cure; it slows progression but does not reverse existing damage or eliminate the disease entirely[3][4].
The development of AMT-130 builds on over three decades of research since the HD gene was identified in 1993. Previous attempts to lower huntingtin protein levels using drugs or other approaches failed to demonstrate clear clinical benefits. The direct delivery of gene therapy into the brain to bypass the blood-brain barrier represents a novel and promising strategy that may open the door to further advances in treating HD and other neurodegenerative diseases[4].
In summary, while Huntington’s disease has not been cured in 2025, the advent of AMT-130 gene therapy marks a historic breakthrough by demonstrating for the first time that the progression of HD can be significantly slowed. Ongoing research and larger clinical trials will be critical to fully establish the therapy’s long-term benefits and safety profile, but the results to date offer hope to the HD community that a meaningful treatment altering the disease course is finally within reach[1][2][3][4][5].
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Sources:
[1] University of Alabama at Birmingham, “Breakthrough in Huntington’s disease treatment shows unprecedented results for patients,” 2025.
[2] HDBuzz, “AMT-130 Gene Therapy Slows Huntington’s in Landmark Trial,” September 2025.
[3] Nature, “Huntington’s disease treated for first time using gene therapy,” 2025.
[4] UNSW Newsroom, “A new treatment for Huntington’s disease is genuinely promising but here’s why we still need caution,” 2025.
[5] ScienceAlert, “Huntington’s Breakthrough May Not Be The Success It Seems,” 2025.
