By: LIMAT HAILE ’27
Updated 11:50 a.m. EDT, 10 Oct 2025
Huntington’s Disease (HD) is an inherited, relentless and fatal neurodegenerative disorder for which there has been no cure. For families affected by the condition, there is the certainty of decline stretching across generations, meaning that the inherited gene will cause the mind and body of the affected individual to slowly unravel. HD is a rare but devastating condition, affecting hundreds of thousands worldwide. Symptoms usually start in mid-life, often between the ages of 30 and 50, and include involuntary, uncontrollable movements, depression, irritability and a progressive decline in thinking and memory. Patients gradually lose the ability to live independently. Most affected individuals die 10 to 20 years after symptoms first appear.
The cause of this devastating illness is a single genetic mutation: an expanded stretch of certain DNA repeats (CAG) in the huntingtin gene (HTT). This mutation results in an oversized, faulty protein that gradually destroys specific nerve cells, known as “medium spiny neurons,” particularly in the brain’s striatum. Although the causative gene was identified in 1993, three decades of attempts to develop effective therapies have failed to show convincing clinical benefits.
Now, a new treatment is being widely reported as a breakthrough. The experimental treatment, called AMT-130, is a one-time gene therapy developed by uniQure, a company based in the Netherlands and the United States (US). The treatment is highly invasive, requiring lengthy brain surgery, sometimes lasting 8 to 14 hours, to infuse an engineered adeno-associated virus directly into the caudate and putamen brain regions. The virus acts as a shuttle, carrying a short genetic “microRNA” designed to specifically target and degrade the messenger RNA (mRNA) that carries the instructions for building the mutant huntingtin protein, thereby aiming to lower the toxic protein levels.
The Phase I/II clinical trial began with 29 patients with early HD, but only 24 participants completed the 36-month trial. The treated participants were divided into low-dose and high-dose groups, with 12 patients in each group. Early results from this trial, conducted in the US, the United Kingdom (UK) and Europe, suggest the treatment significantly slows the disease’s progression. The UK arm of this study was supported by the National Institute for Health and Care Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC). According to uniQure, which funded the study, patients who received the higher dose of AMT-130 declined more slowly than expected. Participants who received a higher dose were reported to have a 75% slowing in their decline. The company claims that the new treatment slows the decline so effectively that what typically happens by a year takes four; this was measured against a matched external control group from a global Huntington’s registry.
Furthermore, on the Total Functioning Capacity (TFC) scale, which assesses independence in daily living, a 60% slowing in decline was reported for the higher dose group. Lead researcher Professor Sarah Tabrizi, supported by the BRC, stated that these “groundbreaking data are the most convincing in the field to date,” underscoring potential disease-modifying effects.
However, caution remains essential. Bryce Vissel, Cojoint Professor at the University of New South Wales Sydney, notes that the results are early, unreviewed and rely on external comparisons rather than a randomized placebo group, a design which can introduce bias. The patient numbers are also small—only 12 patients were in the high-dose group at the three-year mark—meaning solid conclusions cannot yet be drawn. If the results are upheld, this complex neurosurgical treatment would represent the first convincing evidence that a gene-targeted therapy can slow HD. UniQure has stated plans to seek regulatory approval as early as 2026. ★
