New treatment slows Huntington’s disease for the first time

Scientists have slowed the progression of Huntington’s disease for the first time with a “groundbreaking” new treatment.

Experts from University College London (UCL) said the finding could “change everything” for patients with the condition, which gets worse over time and has no cure.

The disease affects movement, thinking and mood.

The study tested a new gene therapy, AMT-130, which is delivered by brain surgery.

The early stage clinical trials among 29 patients concluded that those who were given a high dose of the treatment experienced 75% less disease progression after 36 months, according to uniQure, a gene therapy company based in the Netherlands and the US.

A single dose is is expected to last for a person’s life.

“This result changes everything,” said principal investigator Professor Ed Wild, from the UCL Huntington’s Disease Centre.

“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.

“If that happens, we need to work hard to make it available to everyone who needs it, while working no less diligently to add more effective treatments to the list.

“Trial results come through in numbers and graphs, but behind each datapoint is an incredible patient who volunteered to undergo major neurosurgery to be treated with the first gene therapy we’ve ever tested in Huntington’s disease. That is an extraordinary act of bravery for the benefit of humanity.

“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.”

The lead scientific adviser on the trial, Professor Sarah Tabrizi from UCL Huntington’s Disease Centre, said: “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.

“For patients, AMT-130 has the potential to preserve daily function, keep them in work longer, and meaningfully slow disease progression.”

Huntington’s disease is a fatal neurodegenerative disease caused by a single genetic mutation.

Jack May-Davis, 30, from Sussex, found out that he carried the Huntington’s Disease gene when he was 19.

Two of his family members have died from the condition, including his father.

Since finding out he carries the gene, Mr May-Davis has been involved with trials at the National Hospital for Neurology and Neurosurgery at University College London Hospitals.

“The results are astonishing – I’m lost for words,” he said.

“It is just amazing.

“When I started participating in trials I never thought something would be developed in a timeframe that might be actually be useful for me.

“This feels like a huge moment that will mean so much to families who carry the Huntington’s gene.”

In the trial, some 12 patients were given the highest dose of AMT-130.

Among this group, researchers reported that they experienced 75% less disease progression after 36 months compared to a group of people with Huntington’s who were not given the treatment.

This was measured via a disease rating scale examining major symptoms of the disease.

Researchers also measured levels of a protein that is released into the spinal fluid when neurons are injured, known as neurofilament light protein.

They found that levels of this protein were lower among people treated with the drug compared to the levels they had at the start of the trial.

Patients would usually expect to see levels of this protein increase by 20-30% over three years.

Experts said the finding suggests that the disease has been modified and neuronal damage slowed.

They also reported that the treatment is generally well tolerated by patients.

Researchers said that AMT-130 works by permanently introducing new functional DNA into a person’s cells.

It is delivered via particles of an “empty” virus which include a set of instructions encoded in custom-made DNA.

This is injected directly into a part of the brain called the striatum.

Researchers say that when AMT-130 RNA binds to the cell’s own huntingtin RNA, it summons an enzyme to destroy it.

As a result, less of the protein is made.

Professor Mike Hanna, director of the UCL Queen Square Institute of Neurology, said: “These findings point to a new chapter in gene therapy development for Huntington’s disease, and have clear relevance for other devastating neurodegenerative disorders.”

Dr Walid Abi-Saab, chief medical officer of uniQure, added: “We are incredibly excited about these topline results and what they may represent for individuals and families affected by Huntington’s disease.

“These findings reinforce our conviction that AMT-130 has the potential to fundamentally transform the treatment landscape for Huntington’s disease, while also providing important evidence supporting one-time, precision-delivered gene therapies for the treatment of neurological disorders.”

UniQure said it plans to submit an application to the US Food and Drug Administration early next year requesting accelerated approval to market the drug, with applications in the UK and in Europe to follow.

Around 8,000 people in the UK are living with Huntington’s.

The disease typically lasts around 20 years from the onset of neurological problems to death, but disability and loss of function happen early Disability and loss of function happen fairly early on, leading to the need for intensive multidisciplinary care for decades.

Cath Staney, chief executive of the Huntington’s Disease Association, said: “This is a significant breakthrough, and I am sure it will bring hope to anyone affected by Huntington’s disease.

“This trial shows an astonishing 75% slowing of progression in the disease.

“That is remarkable and will bring much-needed optimism to the Huntington’s disease community.”

Prof Zosia Miedzybrodzka, from the University of Aberdeen, said: “This a very exciting and important breakthrough.

“However, it is still early days and a lot more testing is needed to see if there are side effects of this new gene therapy, how long the benefits last and how well it works in the long term.

“But this is a groundbreaking first step and a day to celebrate.”

Prof Siddharthan Chandran, director of the UK Dementia Research Institute, said: “We’ll need to wait for the full peer-reviewed results to come out, but this is promising and gives real hope to families dealing with this disease.

“The next step is getting this drug into larger, late-stage trials.”