Gene therapy for Huntington’s disease showed great promise in 2025

This year marked a pivotal moment in the quest to treat Huntington’s disease, a rare but devastating form of dementia. Scientists have discovered that an experimental gene therapy slows the progression of the disease – the first time this has been achieved. While this is a huge feat, implementing the therapy remains a challenge, which is why researchers are already working on a more practical intervention.

“This is a giant step forward,” says team member Sarah Tabrizi from University College London, referring to the success of the existing therapy in a late-stage trial earlier this year. “That tells you that Huntington’s disease has the potential to be treatable. That gives us a huge window of opportunity.”

Huntington’s disease is caused by a genetic mutation that causes the normally harmless huntingtin protein to build up in toxic clumps inside the brain. Over time, this kills brain cells, leading to difficulty with movement, thinking, and mood. There are no approved treatments that prevent symptoms from getting worse, with interventions instead focused on supporting people through the process.

But the experimental therapy, known as AMT-130, targets these abnormal proteins by delivering genetic instructions to brain cells, instructing them to make a molecule that blocks their production.

In the trial, Tabrizi and colleagues gave a high dose of treatment to 17 people with Huntington’s disease, then compared their cognition, movement, and daily functioning with those of untreated individuals three years later. The drug’s developer, biotechnology company uniQure, shared preliminary results in September, which showed the treatment slowed disease progression by about 75 percent on average.

“We’ve had a lot of setbacks in Huntington’s disease therapies over the last couple of years,” says Sarah O’Shea of ​​Mount Sinai in New York, who was not involved in the research. “So it was huge, not only because it’s a major breakthrough in terms of slowing the progression of the disease, but also [because] it came at a time when we really needed that hope.

However, the treatment is not without its drawbacks. It is delivered deep into the brain during a 12- to 18-hour surgery — something that only a few facilities are capable of performing, even in countries like the United States and the United Kingdom, Tabrizi says. Additionally, if approved for use, it would almost certainly be exorbitantly priced. “So, do I think this will reach everyone? It’s going to be a challenge,” she said.

To get around this problem, she and her colleagues have since developed a similar treatment that is injected into the fluid surrounding the spinal cord. “It is currently a phase I study. We administered the first patient in November 2024,” explains Tabrizi, emphasizing that the results, which should inform us about the safety of the approach, are expected around July 2026.

Meanwhile, UniQure executives said in September that they planned to submit AMT-130 to the U.S. Food and Drug Administration (FDA) for approval in early 2026. But in a November statement, they said the submission timeline was now unclear after the FDA expressed reservations about the study design, particularly its makeshift control group, made up of individuals drawn from a database of people with Huntington’s disease who received no intervention.

The absence of a control group within the trial makes it difficult to know to what extent the placebo effect may have influenced the results. But the invasive nature of the surgery makes it difficult to justify creating such a group.

“We strongly believe that AMT-130 has the potential to deliver substantial benefits to patients, and we remain fully committed to working with the FDA to determine the best path forward to quickly bring AMT-130 to patients and their families in the United States,” Matt Kapusta, CEO of uniQure, said in the release.