Huntington's disease successfully treated for first time

According to doctors, a new gene therapy has for the first time successfully treated Huntington's, one of the most deadly and fatal disorders. The disease, which is inherited, relentlessly kills brain cells and mimics a combination of dementia, Parkinson's, and motor neurone disease. An emotional research team became tearful as they explained how data showed the disease was slowed by 75% in patients.

Professor Sarah Tabrizi of BBC News said the decline you would normally expect in one year will now take four years after treatment, giving patients decades of "good quality life." The latest therapy is a form of gene therapy administered during 12 to 18 hours of delicate brain surgery.

Understanding the Impact

Huntington's disease is usually fatal for patients in their 30s or 40s. Professor Tabrizi, the director of the University College London (UCL) Huntington's Disease Centre, described the findings as "spectacular." She said, "We never in our wildest dreams would have predicted a 75% decline in clinical progression."

None of the patients who have been hospitalised are being identified, but one has been medically discharged and is back at work. Despite being expected to need a wheelchair, many of the participants in the trial are still walking. The treatment is likely to be very expensive. However, this is a moment of real hope for a disease that affects people in their prime and devastates families.

The disease runs through Jack May-Davis' family. He has the defective gene, as did his father, Fred, and paternal grandmother, Joyce. Jack said it was "very sad" to see his dad's inexorable decline. Fred was in his late 30s when the first signs appeared, including behavioural changes and the way he moved. He later needed 24/7 palliative care before he died at the age of 54 in 2016.

Jack, a 30-year-old barrister's clerk, recently married Chloe and has been actively involved in the UCL study to turn his diagnosis into a positive. He had always known he was destined to follow his father's fate. Now, he says the "complete breakthrough" has left him "overwhelmed" and able to look forward to a future that "seems a little bit better." However, he added, "it does not mean that my life will be much longer."

How the Therapy Works

Huntington's disease is caused by an error in a section of our DNA called the huntingtin gene. If one of your parents has the disease, there's a 50% chance you will inherit the faulty gene and develop the condition. This mutation converts a normal protein present in the brain—the huntingtin protein—into a neuron killer. The aim of the therapy is to eliminate this harmful protein in a single dose. The therapy uses cutting-edge genetic medicine, including gene therapy and gene silencing technologies.

It begins with a safe virus that has been modified to include a specially engineered sequence of DNA. This is embedded deep into the brain using real-time MRI scanning, which can direct a microcatheter to two brain regions: the caudate nucleus and the putamen. The neurosurgery can take anywhere from 12 to 18 hours. The virus then acts like a microscopic postman, delivering a new piece of DNA inside the brain cells, where it becomes active. The neurons are turned into a factory for making the medication to prevent their own death.

The cells produce a small piece of genetic material (called microRNA) that is intended to intercept and block the instructions (called messenger RNA) sent from the cells' DNA for creating mutant huntingtin. This has resulted in lower amounts of mutant huntingtin in the brain.

Trial Results and Future Outlook

The findings from the trial, which involved 29 patients, have been announced in a statement by the company UniQure, but they have not yet been published in full for peer review. According to the results, there was an average 75% decline in the disease three years after surgery, based on a system that integrates cognition, motor control, and the ability to cope in daily life.

The results also show that the therapy is saving brain cells. Levels of neurofilaments in spinal fluid—a clear sign of brain cells dying—should have increased by a third if the disease continued to progress, but they were actually lower than at the start of the trial.

Professor Ed Wild, a consultant neurologist at the National Hospital for Neurology and Neurosurgery at UCLH, said, "This is the end we've been waiting for... We had every intention that we would never see a result like this." The author of the article added, "living in a world where we know this is not only possible, but it's impossible to fully encapsulate the emotion. He was a bit teary" over the effects it might have on families.

The therapy was deemed safe, but some patients did experience inflammation from the virus that caused headaches and confusion, which required steroid therapy. Brain cells are not replaced by the body in the same way as blood, bone, and skin are constantly refreshed, according to Professor Wild.

Around 75,000 people in the UK, the United States, and Europe have Huntington's disease, with hundreds of thousands more living with the mutation, indicating they will get the disease. UniQure intends to apply for a licence in the US in the first quarter of 2026, with the aim of launching the drug later that year. UK and European authorities will begin next year, but the initial focus will be on the US.

Dr. Walid Abi-Saab, the chief medical officer at UniQure, expressed excitement over the findings, stating the therapy had "the ability to fundamentally change" Huntington's disease. However, the drug will not be available to everyone due to the highly complicated surgery and the anticipated price. Professor Wild said, "It will be expensive for sure."

There isn't a set price for the drug yet. Gene therapy treatments are often expensive, but their long-term results can make them affordable. However, the NHS does not currently pay for a £2.6m-per-patient gene therapy for haemophilia B.

Professor Tabrizi says this gene therapy is "the start" and will open the doors for therapies that can reach more people. She expressed admiration for the patients and families involved in the trial, saying she was "overjoyed for the patients and families." She is currently working with a group of young people who have confirmed they have the gene but don't yet have symptoms—stage zero Huntington's—and is hoping to perform the first prevention trial to see if the disease can be significantly reduced or even stopped completely.