Huntington's: How AMT-130 Gene Therapy Significantly Slows the Disease

Liputan6.com, Jakarta In September 2025, the medical world was shocked by the news of a significant breakthrough in the treatment of Huntington's Disease (HD).

An experimental gene therapy called AMT-130, developed by uniQure, demonstrated remarkable effectiveness in slowing the progression of this genetic neurodegenerative disease.

A clinical trial of AMT-130 gene therapy reported that disease progression could be slowed by approximately 75% over three years in participants.

This was a historic achievement because, unlike previous treatments that only managed symptoms, AMT-130 targeted the root cause of the disease by silencing the mutant huntingtin protein.

The therapy involved a single injection into the brain through a complex surgery, but it was expected to provide lifelong therapeutic effects.

🚨 The first disease-modifying therapy for Huntington's disease was just announced this morning.75% reduction in symptoms over 36 months.This isn't hype.It's field-changing.And it uses RNA.Here's what you need to know about $QURE AMT-130 🧵 pic.twitter.com/WwTuxBvmJb

— Robert Y. Chen (@therealRYC) September 24, 2025

The experimental gene therapy AMT-130 made headlines in September 2025 after showing promising results in clinical trials.

The therapy successfully slowed the progression of Huntington's disease by approximately 75% over three years in participants, marking a significant advance in the treatment of this condition.

Prof Sarah Tabrizi, the director of University College London’s Huntington’s disease centre, who led the trial, said: “We now have a treatment for one of the world’s more terrible diseases. This is absolutely huge. I’m really overjoyed.”

Huntington's runs through Jack May-Davis' family. He has the faulty gene that causes the disease, as did his dad, Fred, and his grandmother, Joyce.

Jack said it was "really awful and horrible" watching his dad's inexorable decline.

AMT-130 works by targeting the root cause of the disease: the harmful mutant huntingtin protein.

By administering a harmless virus carrying genetic material, the therapy effectively silences the production of the mutant protein, thereby reducing nerve cell damage.

In April 2025, the US Food and Drug Administration (FDA) granted Breakthrough Therapy designation to AMT-130.

uniQure plans to submit a Biologics License Application (BLA) in the first quarter of 2026, with the expectation of a US launch by the end of the following year, pending regulatory approval.

It is estimated that there are between 6,000 and 10,000 people with Huntington's disease in the UK, and at least 20,000 more are carriers of the defective gene, meaning they are highly likely to develop it.

However, only around a fifth of affected families choose to be tested for the gene because current treatments only help relieve symptoms, rather than slow the disease's uncontrolled progression.

Huntington’s disease is brutal.A single DNA error → toxic protein → dead brain cells.No cure. Always fatal. Always inherited.But now? Science has flipped the script.How the new gene therapy works:1️⃣ Huntington’s mutation makes a toxic protein that kills neurons.2️⃣… pic.twitter.com/duPjZkVkp6

— Simon Maechling (@simonmaechling) September 24, 2025

Huntington's disease (HD) is an inherited genetic neurodegenerative disorder that causes nerve cells in the brain to gradually damage and die.

This condition significantly affects a person's movement, thinking ability, and mental health, making it a significant challenge for patients and their families.

The primary cause of HD is a mutation in the gene for a protein called Huntingtin.

This genetic defect causes the building blocks of DNA, cytosine, adenine, and guanine (CAG), to repeat many times more than normal, damaging neurons in areas of the brain that control voluntary movement and other functions.

As a genetic disease, HD has a clear inheritance pattern.

Each child of a parent with HD has a 50% chance of inheriting the gene for the disease, making it important to understand the genetic risk within a family.

Symptoms of Huntington's disease vary from person to person, but generally develop slowly and worsen over time.

Symptoms typically begin between the ages of 30 and 50, although they can occur at any age.Movement disorders are a hallmark of HD, which include:

• Involuntary jerking or writhing movements (chorea).
• Muscle stiffness or contractures.
• Difficulty walking or maintaining posture and balance.
• Slow or unusual eye movements.

In addition, people with HD also experience cognitive impairment and mental or behavioral problems.

Cognitive impairments can include difficulty organizing, prioritizing, or focusing on tasks, lack of flexibility, and difficulty learning new information.

Meanwhile, mental and behavioral disorders include personality changes, mood swings, depression, irritability, or impulsivity.

In addition to AMT-130, several other therapies for Huntington's disease are also in development and clinical trials.

One such innovation is Skyhawk Therapeutics' SKY-0515, an oral RNA splicing drug that aims to reduce the huntingtin protein by altering the message of the HTT gene.

The Phase 2/3 FALCON-HD trial began in June 2025, with the first patient dosed.

PTC Therapeutics and Novartis are also developing PTC518 (votoplam), a daily orally administered mRNA splicing-modifying therapy.

Other therapies include Life Edit's LETI-101, a CRISPR gene editing system that selectively targets mutant huntingtin proteins, and Spark Therapeutics/Roche's RG6662 (SPK-10001), a one-time AAV gene therapy that aims to lower huntingtin protein levels through brain surgery.

While gene therapy offers promise, current treatments still focus on managing the symptoms of Huntington's disease to improve patients' quality of life.

To treat chorea, or involuntary movements, medications such as Tetrabenazine (Xenazine), Deutetrabenazine (Austedo), and Ingrezza (valbenazine) have been FDA-approved.

Additionally, antipsychotic medications such as risperidone or olanzapine may be prescribed to manage mood swings, irritability, and psychosis.

Antidepressants and mood stabilizers are also frequently used to treat depression and anxiety, which are common in people with HD.

Sources:

https://www.mayoclinic.org/diseases-conditions/huntingtons-disease/symptoms-causes/syc-20356117

https://www.theguardian.com/science/2025/sep/24/huntingtons-disease-treated-successfully-for-first-time-in-gene-therapy-trial

https://www.nhs.uk/conditions/huntingtons-disease/