Summary of “EHDN Platform Meeting on uniQure topline results: Unpacking the outcomes so far”

Warsaw, November 19th, 2025.

Dear members,

As you might know, yesterday the European Huntington’s Disease Network (EHDN) developed a seminar about the topline results of uniQure, a pharmaceutical company that is currently conducting a clinical trial in a gene therapy product called AMT-130.

But what is gene therapy in this context? How does it work? As we know, Huntington’s disease (HD) is mainly caused by a mutation in the Huntingtin gene. For the past years, researchers have been trying to develop therapies that modify genetic diseases, by delivering special molecules that can “play” with the genes being affected in our organisms. In the HD field, gene therapy aims to modify the disease by targeting its molecular origin. In other words, we want to treat the disease by going to the root of the problem: a defective gene. Prof. Anne Rosser explained to us that AMT-130 is a micro RNA, a very small molecule, that is being delivered directly into the brain of the patients undergoing this clinical trial to lower their Huntingtin protein. This product operates directly in neurons and prevents them from producing more Huntingtin, part of which is toxic (the mutant copy) and causes neural death and therefore HD symptoms. The idea is to receive the AMT-130 once in a lifetime, given that the product can “self-replicate” in the body. So, instead of taking a pill everyday, patients would have to undergo surgery once to receive it. At the moment, this surgery lasts up to 18 hours to be done, as it is very difficult to deliver the product in the exact area of the brain being most affected in HD. In the future, it is expected to find better ways to incorporate this molecule in the body.

The company that is running the trial posted a report in September 2025. This data is publicly available and it presents how the 29 patients that are participating in the study are doing 3 years after their surgery. It is important to remember that this intervention is not a treatment yet, we may still call it “an experiment”, as we need more data and studies to finally get approval for AMT-130.

Prof. Sarah Tabrizi explained more about the clinical trial being discussed. The aim of AMT-130 is to slow the rate of disease progression (meaning, to delay the disease) and to provide HD patients with an improved quality of life. This clinical trial is using data from the observational study Enroll-HD as a control, in other words, it is comparing the results of the patients undergoing surgery with the natural history of the disease (how HD develops normally).

Three years after the intervention, uniQure found that the patients that received a high dose of AMT-130 have a lower progression of the disease, which was assessed by two clinical measurements: the cUHDRS scale and the TFC scale. The cUHDRS showed a reduction in disease progression by 75% and the TFC by 60%. These scales measure motor and cognitive abilities, as well as functional aspects (for example, the ability to work, manage finances or perform daily self-care). Overall, the patients in this study are doing remarkably better in their clinical evaluations than they would do if they had not received the molecule.

What are these results telling us? The panel discussed many aspects. Prof. Tabrizi said that the study is not completed yet and it has some limitations, which is why we need to keep

cautious optimism. It looks like AMT-130 can slow down the disease in a small number of patients, but there is still a lot of research to be done. Prof. Rosser said that these are encouraging results and hopefully more data will be available in the future from the patients that are currently being followed-up. If the results persist, neurosurgeons are optimistic that we can find better ways to deliver the molecule (for example, reducing the time of the surgery). We are in the early days of this chapter for the HD community. Dina De Sousa, an HD patient who also represents the European Huntington’s Association (EHA), said that gene therapy has always been a delicate subject, but she is hopeful that future generations will be helped. We still have a long way down the road, but these are significant results for the HD community. Jenna Heilman from the Huntington’s Disease Youth Organization (HDYO) highlighted that we must have cautious optimism and realistic expectations,the study is really important and has a lot of implications, although families might be conflicted as well (for example, by wanting to support the good news but at the same time grieving their loved ones). Ignacio Muñoz from Factor H said that it is important to have these seminars so families can receive the news from specialists and not the mainstream media. As a scientist, he knows that we do not have access to all the information (like placebo effect, among other aspects). On the other hand, we now know that it is possible to lower the Huntingtin protein directly in the brain and that the intervention is well tolerated. He encourages us to be patient and optimistic. Dr. Patrick Weydt said that we will always have to communicate news with incomplete information, so we have to be careful with terms like “treatment” (which can be interpreted in many ways within the community), considering that we are still talking about experimental interventions.

In the time for questions, it was assessed that researchers need to be in constant contact with the regulatory agencies. Approval procedures take time and resources, we are in need of more data to finally establish a treatment. Overall, we are talking about good news for the HD community, although this is still an open clinical trial. It will take time to gather more evidence and hopefully, if the tendencies seen in the study are maintained, AMT-130 will advance in its consolidation to become a therapy for HD.

We will keep you posted when more information becomes available.

You can watch the full webinar here.

Best wishes,

Victoria Graffe.