First-in-Human Gene Therapy AMT-130 for Huntington’s disease Reports Positive Results in Phase I/II Trial

Huntington’s disease (HD) has remained one of the most challenging inherited neurological disorders, with no approved treatment to slow or stop its progression. Until now, patients and families depend only on therapies that manage symptoms which leaves a major gap in care. Now, new data from UniQure’s pivotal Phase I/II trial of investigational drug AMT-130, the first gene therapy tested in HD has created new hope in this field.

About Huntington’s disease

Huntington’s disease is a rare, inherited neurodegenerative disorder caused by a mutation in the HTT gene. This mutation leads to abnormal production of huntingtin protein, which gradually damages nerve cells in the brain. Symptoms often begin in mid-adulthood and include uncontrolled movements (chorea), cognitive decline, and psychiatric disturbances such as depression and irritability. Over time, the disease persistently progresses, leading to loss of independence and, ultimately, death.

Unlike other conditions where multiple treatment options exist, Huntington’s disease has no therapy that can alter its progression. Current medications only target symptoms such as reducing involuntary movements or treating depression but they do not stop the underlying nerve cell damage. The challenge remains in directly targeting the toxic huntingtin protein and delivering therapies safely into the brain. This has made Huntington’s disease one of the most difficult neurological disorders to treat, warranting urgent research into genetic and molecular approaches.

About AMT-130

AMT-130 is being developed as a one-time treatment that aims to address Huntington’s disease at its root cause. Instead of treating only the symptoms, it is designed to reduce the production of the faulty huntingtin protein that damages brain cells.

The therapy works using a vector virus known as AAV5 (adeno-associated virus type 5). Scientists use this virus as a “carrier” to carry a small genetic instruction into brain cells. These instructions are in the form of a microRNA, which acts like a molecular “switch-off” signal, UniQure leveraging their proprietary miQURE silencing technology for this purpose. Once inside the brain cells, the therapy delivers microRNA molecules that specifically recognize the huntingtin messenger RNA (mRNA). These microRNAs attach to the huntingtin mRNA and block it from being translated into faulty protein. As a result, the cell makes less harmful huntingtin protein.

To deliver AMT-130, neurosurgeons perform a highly targeted procedure, placing the therapy directly into the striatum, a brain region that controls movement and is heavily affected in Huntington’s disease. This direct delivery is important because the therapy needs to reach the exact part of the brain where the damage starts.