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uniQure: AMT-130 Gene Therapy Slows Progression of Huntington’s Disease
- A dose-dependent slowing in Huntington’s disease progression was observed after 24 months in patients receiving high-dose AMT-130.
- The gene therapy was well-tolerated with manageable safety profiles at all doses.
The Latest
The Phase I/II clinical program of AMT-130 consists of two multi-center, dose-escalating clinical trials designed to test the safety, tolerability, and efficacy signals of the gene therapy for treating Huntington’s disease. The trials were conducted in the U.S. (n=26) and Europe/UK (n=13). Twenty-nine patients received one of two doses of AMT-130 (n=12 low dose; n=17 high dose) and 10 control patients received an imitation surgery. From both sites, 24-month follow-up data from a total of 21 patients (n=12 low dose;n=9 high dose) were analyzed for clinical outcomes and compared with an expanded, propensity-weighted external control (n=154) from the Cure Huntington’s Disease Initiative’s database of natural history studies. Results showed that at 24 months, the mean change in the composite Unified Huntington’s Disease Rating Scale (cUHDRS) for patients receiving high-dose AMT-130 was -0.2 compared to -1.0 for control patients; demonstrating an 80% slowing of disease progression. For patients given low-dose AMT-130, their cUDHRS was -0.7 compared to a -1.0, representing a 30% slowing of disease progression. Additionally, a statistically significant reduction of neurofilament light protein, a biomarker of neurodegeneration, was decreased by 11% compared to baseline, further demonstrating a reduction in clinical severity of Huntington’s disease.
Physician’s Perspective
Huntington’s disease is a rare inherited disease that causes progressive degeneration of nerve cells in the brain leading to motor symptoms such as chorea, behavioural abnormalities, and cognitive decline resulting in progressive physical and mental deterioration. According to a 2021 study in Neuroepidemiology, approximately 70,000 people have been diagnosed with Huntington’s disease in the U.S. and Europe, with hundreds of thousands of people at risk of inheriting the autosomal dominant condition. Despite the known pathophysiology that causes the genetic disease, there are currently no known approved therapies to delay the onset or to slow the disease’s progression. AMT-130 is the first therapy to show evidence of a potential long-term clinical benefit and a reduction of a key marker of neurodegeneration.
Molecular Targets
AMT-130 is a type of one-time gene therapy administered through an MRI-guided, convection-enhanced stereotactic neurosurgical procedure into the striatum. Huntington’s disease is caused by a CAG repeat expansion in the first exon of the huntingtin gene that leads to the production and aggregation of abnormal protein in the brain. The therapy consists of two key components: a vector and a gene encoding a microRNA. The AAV5 vector carries an artificial micro-RNA specifically tailored to silence the huntingtin gene, leveraging uniQure’s proprietary miQURE silencing technology. The AAV vector delivers micro-RNAs directly to the brain for non-selective knockdown of both the production of the disease-causing mutant and normal huntingtin protein (HTT).
Company History
uniQure is a biopharmaceutical company based in Amsterdam, Netherlands that is a global leader in gene therapy. The company has already received approvals for gene therapy for hemophilia B after over a decade of research and clinical development. uniQure is now further advancing its pipeline of therapies to include gene therapies for the treatment of patients with Huntington’s disease, refractory temporal lobe epilepsy, ALS, and Fabry disease.
Further Reading: https://uniqure.gcs-web.com/news-releases/news-release-details/uniqure-announces-positive-interim-data-update-demonstrating
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