Huntington’s is a cruel genetic disease that gradually impacts movement, cognition, and memory in midlife—and now, for the first time, there may be hope. A new gene therapy, delivered in a single, one-time injection directly into the brain, has already shown impressive results in initial trials. Are we approaching a real breakthrough in the treatment of Huntington’s disease?

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Huntington’s disease is one of the most severe genetic disorders in modern medicine, and it remains incurable. It affects tens of thousands of people and usually emerges between the ages of 30 and 50. The disease progresses slowly and relentlessly, causing a gradual loss of control over movement, thinking, memory, and emotions until the patient can no longer care for themselves. Most patients live 15–20 years after diagnosis, and death typically results from complications such as infections or poor nutrition [1]. Current treatments focus only on relieving symptoms: drugs that alleviate involuntary movements, antidepressants, medications for anxiety and psychosis, along with physical therapy and occupational therapy. None of these approaches slows or halts the disease itself.

At the root of the disease lies a single, relatively simple gene called HTT, which contains a short, three-letter DNA sequence that repeats: C-A-G. In a healthy body, the sequence repeats 35 times or fewer; in people who will develop the disease it repeats 39 times or more. This produces an elongated, deformed protein: mutant huntingtin. The toxic protein accumulates in brain cells like hazardous waste, slowly destroying them and disrupting neural activity [3]. The longer the repeat, the earlier the disease starts and the faster it progresses. Huntington’s is an autosomal-dominant disease: inheriting a single defective gene from either parent is enough to cause it. Since the gene’s discovery in 1993, the defective gene can be detected with a simple blood test, but that knowledge also causes great pain and raises difficult questions.

Damage begins in a small yet critical brain region, the striatum, which controls movement. The striatum is also one of the main regions affected in Parkinson’s disease, well known for its dramatic impact on motor ability. Neurons in the striatum die gradually, and the destruction later spreads to the cerebral cortex (responsible for thinking and planning) and to the connections between the striatum and other brain areas. The visible outcome is involuntary movements called chorea, tremors, muscle rigidity, and difficulty walking, speaking, and swallowing.

However, many years before motor symptoms appear—sometimes 15 to 25 years—early signs emerge: declining concentration, memory impairment, difficulty in switching between tasks (cognitive rigidity), mood changes, depression, and anxiety. Although the person still feels “perfectly healthy,” the brain has already begun to change [3]. These early changes create a decades-long window of opportunity in which intervention might prevent damage before the full onset of the disease.

Enter the new therapy, AMT-130, developed by uniQure. It is the first gene therapy for Huntington’s disease to reach human trials. The treatment uses a safe viral vector to deliver DNA that encodes an artificial microRNA [6] into the brain. This microRNA binds to the HTT messenger RNA and shuts down production of the toxic protein. The cells continue to produce the microRNA indefinitely, lowering the level of the mutant protein over time [4]. Preclinical studies in mouse and pig models [7, 8] showed that the therapy significantly and durably reduces mutant protein levels, lowers its accumulation, improves motor and cognitive function, and slows neurodegeneration—even when the disease is already advancing. The safety of the brain-injection technique was tested in a study on monkeys [9] before receiving approval for human clinical trials.

AMT-130 is administered only once, in a precise surgical procedure under general anesthesia. Physicians inject the genetic material directly into the striatum through a thin needle, with minimally invasive surgery, guided by real-time MRI.

In an initial phase 1/2 trial involving 29 diagnosed patients, some participants received a low dose and others a high dose. According to company reports released in September 2025, the high-dose group exhibited about a 75 percent slowdown in disease progression over three years compared with an external control group (data from similar untreated patients in a patient registry), across various functional measures. In addition, levels of the toxic protein in the cerebrospinal fluid decreased. It is important to note that the therapy is not a cure, and the data are still preliminary and have not yet been published in a peer-reviewed journal [4].

As of March 2026, the U.S. Food and Drug Administration (FDA) ruled that while the data are impressive, they are insufficient for approval of the therapy. The main reason is that the trial lacked an internal control group; relying on an external control is too weak to confirm that the delayed progression results from the treatment and not from other differences between the groups. Therefore, the FDA requires a larger, randomized, controlled phase 3 trial in which patients will be assigned to two groups: one will receive the actual therapy, and the control group will undergo a sham surgery without active injection. Only this design can provide a proper comparison under similar conditions.

The company plans another meeting with the FDA in the second quarter of 2026 to discuss the next trial’s design and will add longer-term follow-up data (up to four years). This does not mean the therapy has failed—the early results are promising—but they must faithfully reflect a true therapeutic effect. The road to approval is still long, and the FDA mandates stringent control standards [5].

The excitement arises because, for the first time, a therapy may alter the course of the disease rather than merely ease its symptoms. In the future, it might be possible to treat much earlier, even in young people who have only just learned they have the defective gene, before any damage starts. And this is not the end: researchers are already developing more advanced approaches, such as CRISPR-based gene editing that “cuts out” the defective repeats, or treatments that target only the mutant protein [10].

For families who have lived for generations under Huntington’s grim shadow, this news offers real, evidence-based hope. The disease is still incurable, but for the first time there appears to be a therapy that can slow its progression.

Hebrew editing: Smadar Raban
English editing: Elee Shimshoni

References:

1. Review of the prevalence of Huntington’s disease in the global population
2. Overview of the disease and the new therapy
3. Review article on the disease and current and prospective treatments
4. Preliminary results of the AMT-130 trial – official uniQure release
5. Company regulatory update on the new therapy
6. On the Nobel Prize awarded for the discovery of micro-RNA
7. Study testing the therapy in a mouse model
8. Preclinical study of the therapy in a pig model
9. Study on the safety of direct brain injection in monkeys
10. Review of new CRISPR-based treatments for neurodegenerative diseases