First evidence that gene therapy can slow Huntington's disease

A microRNA treatment is the first therapy to show evidence of slowing Huntington's disease progression.

In a global phase I/II clinical trial, led by researchers at University College London (UCL), researchers have shown that a one-time 'high dose' of AMT-130, which lowers the huntingtin protein (HTT), slowed Huntington's disease progression by 75 percent over a three-year period in 12 gene carriers. Measured by the composite Unified Huntington's Disease Rating Scale, which assesses both motor and cognitive function, the therapy suggests broad symptom delay.

'I believe these groundbreaking data are the most convincing in the field to date and underscore potential disease-modifying effects in Huntington's disease, where an urgent need persists,' said Professor Sarah Tabrizi, director of the UCL Huntington's disease centre.

AMT-130 is delivered via a 14–18 hour neurosurgical procedure, during which a viral vector carrying a microRNA is injected directly into the striatum, the brain region most affected in Huntington's disease. Rather than editing DNA, the therapy degrades HTT mRNA before it can produce the toxic protein.

Other measurements also indicated that disease progression was impacted: total functional capacity decline slowed by 60 percent, and levels of the biomarker neurofilament light, which typically rise with Huntington's disease progression, decreased by 8.2 percent.

Dr Walid Abi-Saab, chief medical officer of uniQure, which developed the treatment, said: 'These findings reinforce our conviction that AMT-130 has the potential to fundamentally transform the treatment landscape for Huntington's disease, while also providing important evidence supporting one-time, precision-delivered gene therapies for the treatment of neurological disorders.'

While promising, assessment of the forthcoming peer-reviewed publication will be crucial to determine participant variability and confirm the durability of these effects. Notably, the study compared results against data from the ENROLL-HD cohort rather than a placebo group, given ethical concerns with sham neurosurgery. The impact of this choice on measured efficacy remains to be clarified.

Despite these caveats, the findings mark a breakthrough for the Huntington's disease community. uniQure plans to launch AMT-130 in the USA in 2026, followed by filings in the EU and UK, potentially being the first approved treatment to alter the course of the disease.

Professor Siddharthan Chandran, director of the UK Dementia Research Institute, said: 'This is incredible news for everyone affected by Huntington's, a cruel and devastating disease.'