Gene Therapy AMT-130 Shows Promising Results in Slowing Huntington's Disease Progression

A groundbreaking gene therapy, AMT-130, has demonstrated significant potential in slowing the progression of Huntington's disease by an impressive 75%, according to recent findings. Developed by uniQure, this treatment represents a major scientific advancement for the devastating hereditary neurodegenerative disorder, which has historically offered very limited therapeutic options for patients, as reported by uniqure on September 24, 2025.

The positive topline data emerged from a pivotal Phase I/II clinical study, where high-dose AMT-130 met its primary endpoint by significantly slowing disease progression over 36 months. This outcome provides substantial hope for the affected community, marking a potential shift in how the disease could be managed, uniqure announced on September 24, 2025.

Huntington's disease is a rare, fatal genetic condition characterized by progressive degeneration of nerve cells, leading to severe motor, cognitive, and psychiatric symptoms. Currently, no approved treatments can alter the disease's course, with existing therapies only managing symptoms, as highlighted by the Mayo Clinic on April 25, 2024.

AMT-130 works by delivering an artificial microRNA directly into the brain, designed to silence the huntingtin gene responsible for producing the toxic protein that causes the disease. This one-time neurosurgical procedure aims to inhibit the production of the mutant protein, offering a novel approach to treatment, according to uniqure's pipeline description.

While the results are highly encouraging, the regulatory path for AMT-130 has seen recent developments. uniqure reported on November 3, 2025, that the U.S. Food and Drug Administration (FDA) no longer considers the external control data from the Phase I/II studies adequate as primary evidence for a Biologics License Application (BLA) submission, creating uncertainty regarding the timeline for approval.

Despite this regulatory hurdle, the therapy has previously received significant designations, including Breakthrough Therapy, Regenerative Medicine Advanced Therapy (RMAT), and Orphan Drug status. These designations underscore the high unmet medical need and the promising nature of AMT-130's early clinical data, as noted by uniQure in their regulatory updates.

The scientific community, including experts like Dr. Sarah Tabrizi, who led the study, has expressed excitement, describing the results as "the most convincing in the field to date." This sentiment, reported by The BMJ on September 26, 2025, reflects the potential for AMT-130 to offer the first realistic hope of altering the disease course for patients.

• Huntington's Disease: A Devastating Unmet Need

  Huntington's disease (HD) is an inherited neurodegenerative disorder caused by a faulty gene that leads to the production of an abnormal huntingtin protein, damaging brain cells. Symptoms, typically appearing between ages 30 and 50, include involuntary movements (chorea), cognitive decline, and psychiatric issues, progressively worsening over time. There is currently no cure, and existing treatments, such as tetrabenazine, deutetrabenazine, and antipsychotics, only manage symptoms without addressing the underlying disease progression, as detailed by BuzzRx on August 25, 2024.

• AMT-130's Innovative Mechanism of Action

  AMT-130 employs an adeno-associated virus (AAV5) vector to deliver an artificial microRNA (miRNA) directly into the striatum, a brain region critically affected in HD. This miRNA is specifically designed to target and silence the huntingtin gene, thereby reducing the production of the toxic mutant huntingtin protein. This one-time, precision-delivered gene therapy aims to inhibit the disease at its genetic origin, a differentiated approach highlighted by uniQure's program description.

• Compelling Clinical Trial Efficacy Data

  Topline 36-month results from uniQure's pivotal Phase I/II study, with a data cutoff of June 30, 2025, showed that high-dose AMT-130 led to a statistically significant 75% slowing of disease progression as measured by the composite Unified Huntington's Disease Rating Scale (cUHDRS). Additionally, a 60% slowing was observed in Total Functional Capacity (TFC), a key secondary endpoint. These findings, reported by globenewswire on September 24, 2025, were compared against a propensity score-matched external control group.

• Favorable Safety Profile and Administration

  The clinical trials indicated that AMT-130 was generally well-tolerated, exhibiting a manageable safety profile across both low and high doses. The most common adverse events were associated with the neurosurgical administration procedure itself, all of which resolved. Importantly, no new drug-related serious adverse events have been observed since December 2022, according to uniqure's September 24, 2025, announcement. The therapy is delivered via an MRI-guided, convection-enhanced stereotactic neurosurgical procedure directly into the brain.

• Navigating the Regulatory Landscape

  AMT-130 has garnered significant regulatory recognition, including FDA Breakthrough Therapy designation in April 2025 and Regenerative Medicine Advanced Therapy (RMAT) designation in May 2024. However, a recent pre-Biologics License Application (BLA) meeting in November 2025 revealed a shift in the FDA's stance, with the agency no longer agreeing that the external control data from the Phase I/II studies are sufficient for primary evidence in a BLA submission, as uniqure reported on November 3, 2025. This unexpected feedback has made the timing of the BLA submission uncertain.

• Transformative Potential and Future Directions

  The positive results for AMT-130 signify a potential paradigm shift for Huntington's disease treatment, offering the first real prospect of a disease-modifying therapy. While regulatory challenges remain, uniQure has expressed its commitment to working with the FDA to determine a path forward for timely approval. The success of this gene therapy could also pave the way for similar interventions in other neurodegenerative conditions, as suggested by The BMJ on September 26, 2025.

• Distinction from Current Symptomatic Treatments

  Unlike existing medications that merely alleviate symptoms such as chorea, psychiatric disturbances, and cognitive issues, AMT-130 aims to address the root cause of Huntington's disease by reducing the production of the harmful huntingtin protein. This fundamental difference positions AMT-130 as a potential disease-modifying therapy, a critical advancement in a field where current options do not slow or halt disease progression, as noted by Mayo Clinic on April 25, 2024.