In September 24th, the company UniQure announced the results of its clinical trial after 36 months with AMT-130, a gene therapy for Huntington’s disease (HD).
For the first time in a study of this kind, the published results suggest that in a group of patients receiving the highest dose, disease progression stabilized. On average, patients did not worsen in their motor and cognitive abilities, something usually inevitable in Huntington’s disease.Â
While these results are encouraging, it is important to emphasize that this treatment is still in the early stages of research and has a long way to go. Many more studies and official reviews will be needed before it can be approved. Even if approval is eventually granted, there will still be a lengthy process with regulatory authorities before the therapy could become widely available to patients.
AMT-130 is a gene therapy specifically designed to reduce the production of the huntingtin protein, and it’s the first of its kind to be tested in humans.
As we have explained before, HD is caused by a defective version of the huntingtin gene, which contains a DNA sequence that repeats itself (C-A-G). This repetition produces an abnormal form of the huntingtin protein, which gradually damages brain cells.
AMT-130 is an experimental gene therapy that was designed to reduce the amount of huntingtin protein produced by cells. Unlike other treatments taken as pills or via lumbar puncture, AMT-130 is administered directly into the brain in a one-time surgical procedure.
The therapy is carried in a harmless virus (AAV5), which acts as a messenger to deliver new instructions that help brain cells reduce production of the huntingtin protein, including the harmful form responsible for the disease.
This was a Phase I/II clinical study, which means it was the first study to test this treatment in people. In clinical research, at this stage, the main purpose of the study is to evaluate if the treatment is safe and to look for early signs that it might be beneficial.
The study followed participants for three years (36 months) and included people with early-stage HD who received either a low or high dose of AMT-130. The experimental treatment was delivered through brain surgery, performed by an experienced neurosurgical team. The published results focus on 12 participants from the high-dose group who have completed the full 36-month follow-up.Â
Because HD is rare and the administration of the treatments involves brain surgery, this study did not include a placebo group. Instead, researchers used what is known as an external control group, meaning they compared the results of people who received AMT-130 with previously collected data from other individuals with HD who are part of the Enroll-HD database. In studies that use an external control group, participants are matched with people of similar age, symptoms, and disease stage to make the comparison as fair as possible.
To assess how well the treatment might be working researchers looked at standard clinical measures commonly used in HD studies, which evaluate motor, cognitive, and functional abilities. It’s important to note that these results are based on average scores across the group, not on individual outcomes. Because this is a small group of only 12 participants, each person’s data has a big impact on the overall results, meaning some people may have improved more than others.
To assess how the treatment might be working, researchers used the following clinical scales that help determine whether a person’s condition is stable or worsening over time and are widely applied in HD studies:
After three years (36 months) of follow-up, researchers evaluated how participants in both the low-dose and high-dose groups were doing and compared the average results with previously collected data from people in the Enroll-HD database who had not received AMT-130. On average, participants who received the high dose of AMT-130 experienced a greater slowing of disease progression, while the low-dose group showed more variable results. Uniqure believes that these findings suggest a dose-dependent effect, meaning that the higher dose may be more effective.
The strongest effects were seen in overall function, daily activities, and cognitive abilities. The following statistics were observed when comparing the high-dose group with the external control group:
While these results are encouraging, it is important to emphasise that:
The strongest effects were seen in overall function, daily activities, and cognitive abilities. The following statistics were observed when comparing the high-dose group with the external control group:
The key significance of the published results is that they suggest that lowering huntingtin may help modify disease progression. Nonetheless, this is not a cure. AMT-130 remains investigational, is not approved for commercialization, and still has a long way to go in terms of further research and regulatory approvals.Â
This milestone is expected to accelerate research on new therapies and encourage other companies developing treatments with the same strategy, including some in pill form, which could improve global access in the future.
This moment marks a new era in the fight against Huntington’s disease. For the first time, an investigational treatment appears to slow the disease progression in humans.
Patience remains essential: further studies, regulatory approvals, and evaluation of which patient groups may benefit are still needed. The goal is to make future therapies safe, effective, and accessible to all who may benefit.
As always, we extend our sincere and deep gratitude to all clinical trial participants for their courage, and to the researchers working tirelessly to advance science and improve the future for the Huntington’s community.