By: Giselle Acosta
Huntington’s disease has been around for over 100 years, and yet a cure has never been created – until September 24th, 2025. Groundbreaking gene therapy (AMT-130) has shown positive results in slowing the disease’s progression, which is the first time a treatment shows this effect.
Huntington’s Disease is a fatal genetic illness caused by the HTT gene on chromosome 4. It causes a shutdown of neurons, or nerve cells, in the brain. Over time it starts to deteriorate a person’s ability to move, think, and show emotion. Due to its autosomal dominant inheritance pattern, any person whose parent carries this gene has a 50% likelihood of inheriting Huntington’s.
Huntington’s disease symptoms usually appear between the ages of 30-50 but in rare cases can occur earlier or later in life. The disease usually starts to progress 10-25 years after the symptoms begin; these include:
• Involuntary jerking or writhing
• Muscle rigidity
• Impaired coordination
• Difficulty with speech
• Impaired judgement
• Memory decline
• Depression
• Anxiety
• Irritability or aggression
• Obsessive-compulsive behaviors
Huntington’s is confirmed once genetic testing, neurological exam, and brain imaging are all completed.
In a surprising breakthrough, a gene therapy company, uniQure, has announced positive results from a study of gene therapy known as AMT-130. In a one-time dosage, the microRNA presented by AMT-130 is designed to be administered directly into deep brain structures through stereotactic, or image-guided, neurosurgery. This microRNA then binds to the microRNA of the HTT gene transcript, leading to RNA interference, or silencing. This reduces the translation of the huntingtin protein. The reduction in translation of the mutant HTT gene, or the gene that causes Huntington’s Disease, causes a deceleration in the progression of symptoms and onset of the disease. This strategy is known as the non-selective knockdown strategy, it targets both mutant and wild type HTT, rather than focusing only on the mutant allele. This makes it easier to rid of the harmful allele since both are almost identical at the RNA level, so targeting only the mutant alleles is much harder and fails to suppress the allele and its traits effectively.
AMT-130 has just completed its Phase I/II study with positive results. High-dose AMT-130 has been observed to slow the progression of Huntington’s by 75%, slow decline of functional capacity by 60%, and lowered or stabilized biomarkers in treated patients compared to a control group over 36 months.
There are some complications that come with this treatment though:
• Since the procedure is an invasive brain surgery, risks associated with the procedure may arise.
• Non-selective silencing may have adverse effects because knocking down mutant and normal huntingtin proteins comes with the risk of reducing cellular functions, as thenormal protein is known for being involved with transcription regulation, preventing apoptosis, and vesicular and organelle transport.
• It is not yet an approved therapy, meaning it is not available mainstream for all patients suffering from Huntington’s Disease.
UniQure plans to submit a Biologics License Application (BLA), which is a formal request to the FDA to market a biological product for the first time in the U.S, to the U.S Food and Drug Administration (FDA) for accelerated approval by them in early 2026. So far, the FDA has already granted AMT-130 the designations of Breakthrough Therapy Designation and Regenerative Medicine Advanced Therapy (RMAT) based on the potential of AMT-130 to address the major unmet medical need among Huntington’s Disease patients. The RMAT designation allows uniQure to have increased collaboration with FDA to accelerate development, which can give patients earlier access to this treatment.
Overall, AMT-130 is showing promising results in its trial stages, which offers hope for a treatment that goes beyond helping quiet symptoms but targeting the root of the issue. If it gets approval by the FDA, this treatment may be able to transform the lives of approximately 41,000 people in the U.S who have Huntington’s Disease, and the 200,000 others that are at risk for developing it. AMT-130 is a major step in the fight against this genetic disorder!
