Is it for real this time? A statement out of Britain said gene therapy has succeeded for the first time in patients with Huntington's disease, a fatal hereditary brain disorder. Huntington's is a disease in which abnormal proteins accumulate in the brain, destroying body and mind, and there is still no suitable treatment. The gene therapy, while not a cure, was assessed as a breakthrough for slowing disease progression by 75%. Researchers in particular expressed hope that Parkinson's disease and Alzheimer's disease, which have similar causes of onset, could be treated with the same method.
Some experts, however, are holding off on judgment. Eight years ago, news broke that a gene therapy working in a similar way had succeeded, raising great expectations among academia and patients, but it failed to be commercialized later because the efficacy did not meet expectations. There were also views that we should watch a little longer because the clinical trial results have not yet been formally published in a journal.
◇ Blocking disease proteins with short-strand RNA
The Dutch bio corporations uniQure said on the 24th (local time), "In a phase 1/2 trial of 29 patients in the United Kingdom, the one-time gene therapy AMT-130 slowed the progression of Huntington's disease by 75%." The patients were in stage 2 or early stage 3 out of disease stages 0–3. In other words, there were no other treatment options.
Huntington's disease was first reported to academia in 1872 by American physician George Huntington, from whom it takes its name. It typically begins in one's 30s or 40s and, within 15 to 25 years, leads to severe physical and mental incapacity and, ultimately, death. Because patients cannot control their bodies and jerk uncontrollably—appearing to a layperson as if they are dancing—it is also called chorea.
The cause is the huntingtin protein, which is involved in memory storage. If a mutation occurs in the gene that synthesizes this protein, it produces a larger protein than before that aggregates more easily. When such proteins accumulate in the brain, neurons die. uniQure said AMT-130 fundamentally blocks the abnormal protein that causes Huntington's disease.
The gene therapy proceeds by placing therapeutic DNA, a deoxyribonucleic acid, into an adeno-associated virus (AAV) harmless to the human body and injecting it into the brain. DNA genetic information is transcribed only where needed into messenger RNA (mRNA), which produces various proteins that govern life processes. The DNA in AMT-130 synthesizes microRNA in the patient's brain instead of protein.
Short microRNAs bind to other mRNAs and block protein synthesis. Although the mutant gene that causes the disease was not eliminated, blocking the synthesis of toxic proteins prevented the condition from worsening. The UCL team said that among 12 patients who received a high dose of the gene therapy, motor or cognitive function decreased by 0.38 points after three years, compared with a 1.52-point decrease in other Huntington's patients, showing a 75% difference.
Sarah Tabrizi, head of the UCL Huntington's Disease Centre, said, "Lesions that typically progress over one year occurred over four years in patients who received the gene therapy." Protein levels in cerebrospinal fluid indicating brain damage were also 8.2% lower, supporting that the gene therapy slowed the progression of Huntington's disease.
◇ Hopes for application to Parkinson's and Alzheimer's dementia
Walid Abi-Saab, chief medical officer (CMO) at uniQure, said that day, "These results further strengthen our conviction that AMT-130 has the potential to fundamentally change the treatment landscape for Huntington's disease."
Huntington's disease is a rare hereditary disorder that occurs in about 5 to 10 people per 100,000. There are about 75,000 patients in the United States, the United Kingdom, and Europe. In a press release that day, uniQure said it will apply for approval of the gene therapy to the U.S. Food and Drug Administration (FDA) early next year. The company expects it could be launched as early as the end of next year.
Academia assessed the results as a major achievement in treating Huntington's disease. Ole Isacson, a professor at Harvard Medical School in the United States, said in the journal Science that the clinical trial results were "very encouraging." There was also an outlook that it could be applied to other degenerative brain diseases.
David Rubinsztein of the University of Cambridge in the United Kingdom told the Science Media Centre, "If this gene therapy succeeds, it could lead to the development of similar therapies for other neurodegenerative diseases such as Parkinson's or dementia."
Parkinson's disease and Alzheimer's dementia also arise from the accumulation in the brain of proteins in abnormal forms, so, as with treating Huntington's, the idea is to block the protein synthesis pathway in question. Rubinsztein said, "We only need to tune the genetic material to target the toxic proteins that cause brain diseases."
Some, however, were cautious, noting the small study size and the fact that clinical trial data have not yet been published in a journal. Zosia Miedzybrodzka of the University of Aberdeen in the United Kingdom told the Science Media Centre, "The research is still at an early stage, and many more tests are needed to determine whether there are side effects of the new gene therapy, how long the effect lasts, and its long-term efficacy."
◇ U.S. gene therapy failed in phase 3
MicroRNA has raised high hopes as a treatment for intractable diseases, to the point of producing last year's Nobel Prize in physiology or medicine. AMT-130 has demonstrated that potential. Even so, scientists are not immediately convinced about commercialization because similar gene therapies have failed just before commercialization in the past.
Tabrizi, who led this clinical trial, announced in 2017 that a gene therapy developed by U.S. company Ionis Pharmaceuticals slowed the progression of Huntington's disease. Two years later, a paper was published in an international journal. This gene therapy was transferred to the Swiss global drugmaker Roche and advanced to the final phase 3 trial, but results were worse than in patients given a placebo, and development was halted in 2021.
Harvard Medical School's Isacson said, "Ionis's gene therapy was administered into the cerebrospinal fluid, so the therapeutic RNA may have been diluted or destroyed by RNA-degrading enzymes." In contrast, uniQure drilled holes in the skull and injected the gene therapy directly into the caudate nucleus and putamen—the brain regions first affected by Huntington's—avoiding such problems.
For uniQure, the key to commercialization may be price rather than efficacy. Because each patient's gene mutation differs, the therapeutic gene to be placed in the virus and delivered into the body must be made accordingly. As a personalized therapy, manufacturing expense increases. uniQure said the price of the Huntington's therapy will be at a similar level to other gene therapies that cost more than $2 million (2.8 billion won).
References
UCL (2025), https://www.ucl.ac.uk/news/2025/sep/gene-therapy-appears-slow-huntingtons-disease-progression
uniQure (2025), https://www.uniqure.com/investors-media/press-releases
New England Journal of Medicine (2019), DOI: https://doi.org/10.1056/NEJMoa1900907