UniQure: the Highs and Lows of AMT-130

– Written by the Moving Forward team on September 9th 2022

UniQure is a company with an expertise in gene therapy that has long been involved in the search for HD treatment options. Their preclinical studies in animal models showed that AMT-130, the gene therapy product candidate for HD, reduced the mutant huntingtin protein and was associated with a decrease in the progression of Huntington’s disease signs.

The ongoing study with AMT-130 in HD patients started in September 2019 in the US and is also being conducted in Europe. This is a Phase 1/2 study, so it is primarily aimed at finding a safe AMT-130 dose for patients with early manifest HD. Study participants go through a surgical procedure where the drug is injected deep into the brain to inhibit cells from producing the huntingtin protein. Participants are divided into three groups – low-dose AMT-130, high-dose AMT-130 and “control” (people that go through an imitation surgery without drug administration).

The study will look at how the body reacts to the drug, and how well the drug and the procedures are tolerated but will also investigate how AMT-130 relates to disease progression. It is designed to have a five-year duration.

In June, the company shared the 12-month data of 10 patients (six received the low dose of AMT-130 and four did not receive any drug). Overall, the drug and surgery were well tolerated, with no major safety issues arising. Additionally, looking at the levels of huntingtin and other biomarkers of a sub-set of patients, the data suggested that AMT-130 was working as expected, i.e., was lowering the mutant huntingtin levels over time.

Early in August, UniQure has disclosed serious side effects in three of the 14 patients treated with the higher dose of AMT-130. Although the patients have recovered, the need to handle this situation with maximum caution has made UniQure decide to pause the procedures in the high-dose patient group until it has a safety report in the fourth quarter of the year.

This decision will not affect patients in the low-dose group whose “profile remains strong”, says UniQure. So it is expected that in the second quarter of 2023 we can have additional data regarding the 24-month follow-up of these patients.

From an HD family member perspective, we believe that we are stronger together and that mutual support is even more valuable when we have to face trial setbacks. As every fall is followed by a rise, we trust that every new data in HD research gives researchers new space for investigation. Thus, we think that the new information provided by this downside can bring us closer to an effective treatment for HD. The HD community all over the world keeps a close eye on HD research and has an enormous gratitude to all the patients and researchers involved in the AMT-130 trial. We are thankful for all the efforts and personal commitment in the search for a treatment for Huntington’s disease. At the same time, we must not forget that while we strongly wish to find a treatment for HD, our priority is always the health and safety of the brave volunteers who are willing to participate in research. That is why we highly value the trial safety protocols which closely monitor patients and act immediately to safeguard their wellbeing.

In view of all this, the Moving Forward team will pay close attention to the updates about this topic at the next EHDN meeting in September and will share them with the HD patients and families in the near future.

More details about UniQure and AMT-130 can be found here: