[Image created by Claudia Logan with BioRender.com]
Huntington’s Disease (HD) is a rare, inherited brain disorder which progressively damages nerve and muscle functions, yet until recently had no cure. In 2024, roughly 8,000 people were living with Huntington’s in the UK, according to the Huntington’s Disease Association UK. The average age of onset is around 40, and the disease typically leads to a 10-30-year decline in physical, behavioural, and cognitive functions. Severe physical and mental deficits develop soon after onset, requiring intensive long-term care.
At the end of September, a major breakthrough emerged from a clinical trial conducted by uniQure in the EU and the United States. Previous research has shown that mutations in the huntingtin gene (HTT) are solely responsible for the disease. While lifestyle factors, such as physical and cognitive activity, smoking, drinking, diet and BMI, may influence onset, they are unable to prevent the inevitable decline. Targeted medical therapies are needed to address the root genetic cause.
Clinical Trial Results:
UniQure’s global teams have developed AMT-130, a gene therapy designed to silence the mutant HTT (mHTT) gene. Through blocking production of this harmful protein, which normally leads to the breakdown of neurons, this therapy aims to slow disease progression. AMT-130 is the first therapy to produce such promising results in the field. The clinical trial suggests that AMT-130 can slow disease progression by up to 75% in treated patients over 36 months compared with a control group receiving a placebo. Researchers measured progression using two primary metrics: the Total Functional Capacity (TFC) and composite Unified Huntington’s Disease Rating Scale (cUHDRS), which assess motor, cognitive and functional abilities. The trial also measured neurofilament light chain (NfL) protein in the patients’ cerebrospinal fluid, a biomarker for both neuronal damage and dementia disorders. There were significant reductions in the cognitive and functional capacities, and concentrations of NfL in the treatment group after 36 months compared to the control group. There was also a greater effect of the AMT-130 treatment if patients received a high dose compared to a low dose. This suggests that the efficacy of the treatment is dose-dependent. While a high dose of treatment may raise concerns about adverse effects or systemic toxicity, uniQure’s study so far has not reported serious side effects, indicating a strong treatment safety profile.
How the treatment works:
Scientists used a harmless viral vector called AAV5 to deliver AMT-130 into neurons located in the striatum (caudate nucleus and putamen). These regions are most affected by HD, thus silencing the HTT gene here is effective. It delivers its genetic instructions directly into neuronal cells, responsible for maintaining strong connections in the brain that are essential for high-level motor and cognitive functions. These instructions encode a small RNA molecule, called a microRNA (miRNA), that silences the defective mHTT gene in neurons, preventing neuronal damage that would normally cause HD. Specifically, the miRNA binds to mHTT messenger RNA (mRNA), marking it for destruction. By preventing the production of toxic mutant huntingtin protein, AMT-130 reduces neuronal damage and symptoms in HD patients.
Unique benefits of AMT-130:
The treatment has been designed as a one-time therapy due to its long-lasting effects. This, thus, reduces personal and financial stress on families, as well as pressure on healthcare systems like the NHS. Furthermore, this treatment only requires one minimally invasive surgery using an MRI-guided catheter (convection-enhanced delivery) to deliver the therapy directly to specific areas of the brain striatum. This neurosurgical technique does not require highly specialised technology, allowing it to be performed across many developed countries.
A statement from Professor E Wild, who is the principal investigator of the Huntington’s Disease Centre at UCL, expresses the team’s excitement about this breakthrough. “This result changes everything. On the basis of these results it seems likely AMT-130 will be the first licensed treatment to slow Huntington’s Disease, which is truly world-changing stuff, while working no less diligently to add more effective treatments to the list.” [Interview statement from UCL News, 2025]
Future steps to take:
The research teams at uniQure are awaiting regulatory approval to allow public access to AMT-130. Professors involved at UCL and the chief medical officer at uniQure appear optimistic that the FDA will approve their submission in early 2026. While early results are promising, further studies are needed to confirm long-term effects, optimise treatment to increase patient accessibility, and be peer-reviewed in order to strengthen the scientific basis for this treatment. The current clinical trial involved a small cohort of 29 patients, highlighting the need for larger studies. Research into preventative therapies and genetic screening is also expanding and being heavily invested in.
Overall, these advances in genetic therapy for neurodegenerative disorders offer hope that a diagnosis of Huntington’s may no longer mean a lifetime of debilitating symptoms and an inevitable decline. For the first time, there is hope on the horizon as scientists move closer to lasting and effective treatments for HD and other related disorders, such as multiple sclerosis (MS), Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis (ALS).
Article written by Claudia Juliette Logan, a 4th Year Pharmacology, Biomedical Sciences (BSc) student at the University of Edinburgh.
Article edited by Priscilla Wong, a Fourth-Year Biological Sciences (Immunology) student at the University of Edinburgh, and an Online News Editor for EUSci.
Resources:
UCLH (2025) Huntington’s disease gene therapy shows 75 percent slowing in disease progression. NHS UK News, 24 September 2025.
uniQure N.V. (2025) Huntington’s Disease: AMT-130 Programme Pipeline Update. Amsterdam: uniQure N.V., updated October 2025.
uniQure BioPharma B.V. (2025) Safety and Proof-of-Concept (POC) Study with AMT-130 in Adults with Early Manifest Huntington’s Disease. ClinicalTrials.gov Identifier: NCT04120493, updated October 2025.
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