Huntington’s disease is a fatal inherited neurodegenerative disease that affects movement, thinking, and mood. It is often described as a combination of dementia, Parkinson’s disease, and motor neuron disease. The condition is caused by a mutation in the huntingtin gene, which turns the huntingtin protein into a toxic form that gradually kills brain cells.
Symptoms usually begin between the ages of 30 and 50, and the disease is typically fatal within 20 years. If one parent carries the altered gene, their child has a 50% chance of inheriting it and eventually developing Huntington’s disease.
At the University College London (UCL) Huntington’s Disease Centre, Professors Ed Wild and Sarah Tabrizi led the UK arm of a landmark clinical trial testing a one-time gene therapy called AMT-130. The therapy, which requires 12-18 hours of delicate brain surgery, showed a remarkable 75% slowing in disease progression over three years.
Progress was measured through changes in cognition, motor function, and daily living ability. Astonishingly, one patient who had medically retired was able to return to work, while others who were expected to need wheelchairs are still able to walk.
The data also revealed that the treatment appears to be protecting brain cells. Levels of neurofilament light chain (NfL), a biomarker for nerve cell damage, were reduced in the spinal fluid, suggesting less neuronal death compared to what would normally be expected as the disease advances.
AMT-130 works by delivering a small piece of genetic material to silence the faulty huntingtin gene, reducing the accumulation of toxic protein in the brain. This innovative one-time therapy offers genuine hope that the symptoms of Huntington’s disease could one day be delayed or even prevented.
Professor Tabrizi, Director of the UCL Huntington’s Disease Centre, said, “We never in our wildest dreams would have expected a 75% slowing of clinical progression. “ She described the results as “spectacular” (BBC News).
The therapy combines gene therapy and gene-silencing technology, marking a major step forward in genetic medicine. While the treatment is expected to be very costly, it represents a moment of real hope for a disease that strikes people in their prime and devastates families.
There are an estimated 75,000 people living with Huntington’s disease across the UK, US, and Europe, and hundreds of thousands more carry the mutation, meaning they will eventually develop the condition.
The trial sponsor, UniQure, plans to submit an application for regulatory approval in the US in early 2026, with the goal of launching the drug later that year. Discussions with UK and European regulators are expected to begin next year.
How Does Huntington’s Gene Therapy Work?
The therapy uses a harmless virus that has been genetically modified to carry a specially designed piece of DNA. During surgery, doctors infuse this virus deep into the brain, targeting two key regions called the caudate nucleus and the putamen. The procedure takes between 12 and 18 hours and is guided by real-time MRI imaging to ensure precision.
Once delivered, the virus acts like a microscopic postman, delivering the new DNA into brain cells where it becomes active. This transforms the neurons into tiny factories that produce a therapeutic molecule known as microRNA.
The microRNA works by intercepting and disabling the faulty genetic instructions (messenger RNA) that normally tell the cells to produce the toxic form of the huntingtin protein. As a result, the brain produces lower levels of the mutant huntingtin, helping to protect neurons from degeneration.
This sophisticated combination of gene therapy and gene-silencing technology offers a glimpse into the future of precision genetic medicine.
Reference:
BBC News. (2025, October). Huntington’s gene therapy breakthrough. Retrieved from https://www.bbc.co.uk/news/articles/cevz13xkxpro
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