Gene Therapy:

Huntington's Disease

uniQure has demonstrated preclinical proof-of-concept and has submitted an IND in Huntington's disease. 

AMT-130 for Huntington’s Disease (HD)

uniQure is developing a gene therapy for Huntington’s disease (HD), a rare, fatal, neurodegenerative genetic disorder that affects motor function and leads to behavioral symptoms and cognitive decline in young adults, resulting in total physical and mental deterioration. HD is caused by the expansion of CAG trinucleotide in exon 1 of a multifunctional gene coding for protein called huntingtin.

According to the EMA, Huntington’s disease affects approximately 70,000 people in the U.S. and Europe, making this one of the largest clinical unmet needs in the rare disease field. Despite the clear etiology of the disease, there are no therapies available to treat the disease, delay its onset, or slow the progression of a patient's decline.

Our gene therapy product candidate AMT-130 consists of an AAV5 vector carrying an artificial micro-RNA specifically tailored to silence the huntingtin gene, leveraging our proprietary miQURE™ silencing technology. The therapeutic goal is to inhibit the production of the mutant protein (mHTT). Using AAV vectors to deliver micro-RNAs directly to the brain for non-selective knockdown of the huntingtin gene represents a highly innovative and promising approach to treating Huntington’s disease.

In April 2018, uniQure presented an overview of our preclinical data establishing proof-of-concept for AMT-130 (view presentation). Data from multiple preclinical across five animal models show that a single administration of AMT-130 resulted in a dose-dependent and sustained reduction of mutant huntingtin protein (mHTT) in both the deep structures of the brain including the striatum and the putamen, where Huntington’s disease is known to manifest, and the cortex. Once administered, AMT-130 was observed to spread to the cerebral cortex and lowered mHTT in the frontal areas of the brain that show neuropathological changes later in the course of the disease, providing evidence that AMT-130 spread from the injection sites to the cerebral cortex.

A study performed in a large animal model showed that mHTT was significantly reduced by a median of 68% in the striatum and a median of 47% in the frontal cortex at 6 months after administration of AMT-130.

Preclinical studies in rodent models show that the achieved sustained reduction in mHTT resulted in significant improvement of striatal neuronal function, an improvement in motor-coordination, reduced body weight loss, and an increase in median survival by 24%, as compared to the control group.

We are very encouraged by the significant reductions in mutant huntingtin protein, and believe that knock-down of this magnitude has the potential to significantly alter the course of the disease.

The U.S. Food and Drug Administration has granted orphan drug designation for AMT-130 in Huntington’s disease and AMT-130 has received an Orphan Medicinal Product Designation (OMPD) from the European Medicines Agency for the same indication, making it the first investigational AAV-gene therapy in Huntington's disease to receive such designation.  In April 2019, we announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for AMT-130.

The U.S. Food and Drug Administration (FDA) has completed its review of our Investigational New Drug (IND) application for AMT-130, allowing us to begin our planned Phase I/II study.  We expect that in 2019 AMT-130 will be the first one-time administered AAV gene therapy to enter clinical testing for the treatment of Huntington’s disease. 


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