A Rollercoaster Ride to Hope

The AMT-130 Story, and What the FDA's June 2026 Announcement Means for Our Community

Our community’s first meeting with the pharmaceutical company uniQure took place in September 2018. At the time, the idea that a gene therapy could actually slow HD felt like pie in the sky. Nearly eight years later, on June 17, 2026, that hope took a major step toward becoming real.

This update walks through that journey — the excitement, the setbacks, and the advocacy that helped get us here — and what it means going forward.

What is AMT-130?

Gene therapy aims to treat disease by changing the genetic instructions inside our cells. Imagine your DNA is a cookbook. If one recipe contains a mistake, gene therapy works like an editor, correcting or blocking the faulty recipe.

AMT-130 is designed to reduce production of the harmful huntingtin protein that causes HD. It uses a harmless virus to deliver a small genetic molecule into the brain that “switches down” the faulty huntingtin gene. The treatment is given once through MRI-guided brain surgery and has been tested at both a low and a high dose.

So far, AMT-130 has been studied in two Phase I/II clinical trials:

  • United States: Began in June 2020. Participants were randomly assigned to receive either AMT-130 or a sham (imitation) brain surgery.
  • Europe: Began in February 2022 in Warsaw, Poland, and later expanded to sites in the UK. Everyone in this study received AMT-130.

The Journey So Far

  • September 24, 2025 – Landmark results
    Three years after treatment, people who received the high dose of AMT-130 showed a 75% slowing in disease progression compared with matched external controls alongside favourable biomarker changes. You can read more here.

     

  • November 3, 2025 – A difficult reversal
    Following an October 29 pre-submission meeting, the FDA told uniQure it no longer agreed that the trial data — compared against that matched “external control” group rather than an internal placebo group — were sufficient, on their own, to support a Biologics License Application (BLA), the formal request to market AMT-130 in the US.
    This was a major disappointment. A new trial would require more volunteers to undergo brain surgery without receiving the treatment, raising serious ethical concerns for this fatal, progressive disease where every year of delay matters.

     

  • Late 2025 to January 2026 – The community responds
    As they say, “you can’t keep a good man down”: patient advocacy groups in the US quickly mobilised and started 2 petitions which were signed worldwide. On January 22, 2026, with the petitions having gathered more than 48,000 signatures, representatives hand-delivered them to FDA  alongside more than 11,000 messages sent to Congress.The petitions called on the FDA to honour its prior guidance and expedite review by allowing uniQure to file a BLA for accelerated approval consideration for its investigational gene therapy, AMT-130
    Community representatives also secured a place in discussions with the FDA, helping ensure patients’ voices were heard.

     

  • March 2, 2026 – The setback confirmed
    The FDA confirmed its position, saying the existing data were still not enough for approval and again recommending a new randomized, sham-controlled trial.

     

  • April 30, 2026 – Progress in the UK
    While discussions continued in the US, uniQure announced a positive meeting with the UK’s Medicines and Healthcare products Regulatory Agency (MHRA). The company confirmed plans to apply for UK approval in the third quarter of 2026.

     

  • June 17, 2026 – A turning point
    In a major reversal, the FDA and uniQure reached a breakthrough alignment. The FDA agreed to allow uniQure to submit an application for accelerated approval based on the totality of their existing Phase I/II data and three-year follow-up, bypassing the need for a highly controversial sham-surgery study. Read the press release here.

What Happens Next?

It’s important to understand what this does—and doesn’t—mean.

  • AMT-130 is still experimental. It has not yet been approved and is only available through clinical trials.
  • The FDA application has not yet been submitted. uniQure expects to file it in Q3 2026, after which the FDA review process will begin.
  • Accelerated approval is conditional. If granted, it would allow earlier patient access while requiring a follow-up study to confirm the treatment’s long-term benefit.
  • The UK review is happening separately. uniQure also plans to submit its application to the MHRA during Q3 2026.

Even with these important steps still ahead, June 17, 2026 represents a genuine milestone. The achievements are thanks to the trial participants who volunteered for brain surgery, the researchers who continued pushing forward, and a community that refused to give up when the path became more difficult.


For the first time, a treatment has shown in people that it may be possible to slow the progression of Huntington’s disease.

– Article written by Dina de Sousa

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siRNA

A way of silencing genes using specially designed molecules of RNA – like DNA but made of only a single strand – that target the message molecules in cells and tell them not to make a certain protein

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phenoptype

Phenotype refers to an individual’s observable traits, such as height, eye color and blood type. A person’s phenotype is determined by both their genomic makeup (genotype) and environmental factors.

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oxidative seres

an imbalance between unstable molecules called “free radicals” and protective “antioxidants” in your body

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Metabolism & bioenergetics

describe how your body turns food into fuel and uses that energy to live. 

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Small Molecule

a tiny chemical compound, much smaller than big biological structures like proteins, that can easily travel inside our cells to act as medicine (like aspirin or ibuprofen), a building block (like glucose), or a signaling tool in the body, often taken as pills because they’re easy to absorb and distribute

 

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Nucleic acid

(DNA and RNA) are the essential information-carrying molecules in all life, acting like blueprints that store and transmit genetic instructions for building and operating cells, directing everything from growth to protein production, and passing traits from parents to offspring.

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SNP-single nucleotide polymorphisms

a single-letter spelling difference in a gene. SNPs, pronounced ‘snips’, are common and most don’t change the function of the gene.

 
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at risk

You do not know if you carry the genetic mutation for HD gene 

 
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TFC-total functional capacity

A standardized rating scale for function in HD, used to assess capacity to work, handle finances, perform domestic chores and self-care tasks.
Scores range from 0 to 13, with higher scores indicating better functional capacity. 

 
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Double-blinded

 means that neither the participant nor the clinical trial doctor can choose or know the group the participant is in until the trial is over. This approach helps to prevent bias.

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Open label

A trial in which the patient and doctor know what drug is being used. Open label trials are susceptible to bias through placebo effects.

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Gene therapy

a technique that aims to treat or prevent diseases by modifying a person’s genes. It involves introducing, removing, or changing genetic material (DNA or RNA) within a patient’s cells.

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UHDRS- Unified Huntington Disease Rating Scale

A standardized neurological examination that aims to provide a uniform assessment of the clinical features of HD

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CAG repeat

The stretch of DNA at the beginning of the HD gene, which contains the sequence CAG repeated many times, and is abnormally long in people who will develop HD

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Wild-type

the opposite of ‘mutant’. Wild-type huntingtin, for example, is the ‘normal’, ‘healthy’ protein

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Tolerabilty

How well a person can handle a treatment without having serious or uncomfortable side effects.

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Striatum

Part of the brain that  coordinates multiple aspects of cognition, including both motor and action planning, decision-making, motivation, reinforcement, and reward system.

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Randomized allocation

A type of allocation strategy in which participants are assigned to the arms of a clinical trial by chance.

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Radioligand

a radioactive substance that binds to a specific target in the body, allowing visualization of that target’s distribution and activity

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Protein

Protein builds, maintains, and replaces the tissues in your body. The building blocks of life.

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Premanifest / Prodromal

Prior to onset or diagnosis of movement symptoms.

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Placebo

A placebo is a dummy medicine containing no active ingredients. The placebo effect is a psychological effect that causes people to feel better even if they’re taking a pill that doesn’t work.

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PK - Pharmacokinetics

The movement of drugs through the body

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PD - Pharmacodynamics

The body’s biological response to drugs

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PET scan

Positron emission tomography which produces detailed 3-dimensional images of the inside of the body.

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Neuron

Brain cells that store and transmit information

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MRI

Magentic resonance imaging: A technique using powerful magnetic fields to produce detailed images and visualizes the structure of organs, tissues, and bones 

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mHTT

Mutant huntingtin protein. The protein produced by the faulty HD gene.

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Manifest

after HD diagnosis, or when symptoms are already showing

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Longitudinal study

A study where each participant is looked at several times over a time period – unlike a cross-sectional study, where each participant is looked at only once

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HTT

one abbreviation for the gene that causes Huntington’s disease. The same gene is also called HD and IT-15

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fMRI

functional MRI:As with MRI, a technique using powerful magnetic fields  but focusing on brain function by measuring and mapping changes in blood flow, revealing which areas of the brain are active during specific tasks or cognitive processes

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CSF - cerebrospinal fluid

A clear fluid produced by the brain, which surrounds and supports the brain and spinal cord.

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Efficacy

A measure of whether a treatment works or not

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ASO(Antisense oligonucleotides)

A type of gene silencing treatment in which specially designed DNA molecules are used to switch off a gene

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Biomarker

a test of any kind – including blood tests, thinking tests and brain scans – that can measure or predict the progression of a disease like HD. Biomarkers may make clinical trials of new drugs quicker and more reliable

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BDNF

Brain-derived neurotrophic factor: a growth factor that may be able to protect neurons in HD.

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Allele

one of the two copies of a gene

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Plasma

Liquid component of the blood.

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Gene

The basic unit of heredity passed from parent to child. Genes are made up of sequences of DNA and are arranged, one after another, at specific locations on chromosomes in the nucleus of cells.

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Phase

Clinical trial phases are different stages of research that assess the safety and effectiveness of a new medical treatment or intervention in humans.

Each phase has a specific goal and involves a different number of participants. Generally, there are 4 phases (I-IV), with Phase I focusing on safety and dosage, Phase II on efficacy and side effects, Phase III on comparing the new treatment with standard treatments, and Phase IV on long-term safety monitoring.