Doctors have achieved the first successful treatment of Huntington's disease using gene therapy, marking a historic breakthrough for patients facing this devastating hereditary neurological condition. The gene therapy AMT-130, developed by uniQure, slowed disease progression by 75% in patients after three years of treatment, representing the first time a drug trial has reported continuing, statistically significant slowing of Huntington's progression.
Revolutionary Gene Therapy Approach
The treatment targets the root cause of Huntington's disease by inactivating the mutant protein that causes the condition. The therapy is delivered via a harmless virus that has been modified to carry a specifically designed strand of DNA into neurons. This DNA instructs brain cells to block the production of the toxic version of huntingtin protein, which steadily kills brain cells leading to dementia, paralysis and ultimately death.
The complex treatment procedure requires 12 to 20 hours of surgery, during which the virus is infused very slowly through a micro-catheter into two separate brain regions to avoid adverse reactions. Despite the lengthy procedure, patients receive the treatment in a single shot, making it a one-time intervention.
Clinical Trial Results
The trial involved 29 patients treated in the UK and US, with results showing dramatic improvements in disease progression. Three years after treatment, those receiving the high dose demonstrated an average 75% slowing of disease progression based on comprehensive assessments of motor function, cognition and patients' day-to-day life experiences.
Brain imaging revealed clear indicators that neurons were being spared from destruction, with levels of neurofilaments—a biomarker of cell death—being significantly lower in the treatment group compared to controls.
Professor Sarah Tabrizi, director of University College London's Huntington's disease centre and lead scientific advisor on the trial, described the results as "spectacular." She stated: "I am thrilled that this study of AMT-130 showed statistically significant effects on disease progression at 36 months. These groundbreaking data are the most convincing evidence in the field to date and underscore the disease-modifying effect in Huntington's disease, where an urgent need persists."
Impact on Patient Lives
The treatment's potential extends beyond slowing disease progression to preserving patients' quality of life and independence. Professor Tabrizi noted that "for patients, AMT-130 has the potential to preserve daily function, keep them in work longer, and meaningfully slow disease progression."
Professor Ed Wild, principal investigator at the UCL Huntington's Disease Centre, emphasized the transformative nature of these results: "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."
Wild reported observing unprecedented stability in his trial patients, noting: "My patients in the trial are stable over time in a way I'm not used to seeing in Huntington's disease – and one of them is my only medically-retired Huntington's disease patient who has been able to go back to work."
Particular Significance for Scotland
The breakthrough holds special significance for northern Scotland, which has one of the highest rates of Huntington's disease in the world. Recent research by the University of Aberdeen found that northern Scotland has a rate of 14.5 per 100,000 people—more than five times the estimated worldwide rate of 2.71 per 100,000 people.
The study identified more than 160 adults living in Grampian, Highland, Orkney, Shetland, and the Western Isles who carry the gene but have not been tested, with researchers believing the actual figure is even higher as not everyone with symptoms seeks diagnosis.
Disease Background and Genetic Impact
Huntington's disease is a hereditary condition that impacts entire families across generations. Each child of a person with Huntington's disease faces a 50% risk of inheriting the condition. The disease typically begins to develop between ages 20 and 70, with symptoms progressing slowly over 10 to 25 years from onset until death.
The condition resembles a combination of dementia, Parkinson's disease, and motor neurone disease. Patients may eventually lose the ability to walk, talk, eat, drink, make decisions, or care for themselves. First symptoms, typically appearing in patients' 30s or 40s, include mood swings, anger and depression, later progressing to uncontrolled jerky movements, dementia and ultimately paralysis.
Currently, an estimated 6,000 to 10,000 people in the UK have Huntington's disease, with at least another 20,000 carrying the faulty gene. However, only about one-fifth of those in affected families choose genetic testing because previous treatments only addressed symptoms rather than slowing disease progression.
Future Implications and Regulatory Path
The dramatic impact of the therapy raises possibilities for preventing symptoms if administered at earlier stages of the disease. Professor Tabrizi anticipates that "many more people will come forward for the genetic test because there's a treatment."
UniQure's chief medical officer, Walid Abi-Saab, expressed excitement about the results, stating the company hopes to submit the drug for approval in the US early next year. However, the complex surgical delivery method means the treatment will be expensive.
Healthcare System Preparedness
Alistair Haw, CEO of the Scottish Huntington's Association, welcomed the breakthrough while emphasizing the need for healthcare system readiness. "These are the best results to date from any clinical trial aiming to slow the progression of Huntington's disease," he said. "After many years of hope and false dawns, this is a day for rejoicing for the global Huntington's community."
However, Haw warned that increased demand for genetic testing and specialist services will require expanded healthcare capacity, particularly as more people seek testing now that effective treatment is available.
