FDA Clears IND for Huntington Disease Therapy AMT-130


A planned phase 1/2 trial of the recombinant AAV5 vector treatment is expected to begin dosing patients in the second half of 2019.

Matt Kapusta

Matt Kapusta, MBA

The FDA has completed a review of an Investigational New Drug (IND) application for AMT-130 and has given the go-ahead to its developer, uniQure, to begin its planned phase 1/2 trial of the recombinant AAV5 vector.1

The gene therapy carries a DNA cassette which encodes a microRNA that non-selectively lowers, or knocks down, human huntingtin protein in patients with Huntington disease. UniQure’s chief executive officer, Matt Kapusta, MBA, called the IND clearance “a significant milestone for Huntington’s disease patients and an important event in the field of gene therapy.”

Preclinical animal studies of the treatment have demonstrated widespread localization of AMT-130 in the brain and spinal cord of primates after direct injection.2 As well, data showed effective distribution and a prevalent silencing of human mutant huntingtin gene (mHTT) in mini pigs in one of the largest animal models of Huntington available.3 The mini-pig study showed that mHTT was significantly reduced by an average of 68% in the striatum and a median of 47% in the frontal cortex at 6 months after administration of AMT-130.4

As well, in rodent trials, the 1-time delivery of AMT-130 showed dose-dependent vector DNA and microRNA expression, up to 12-months of lowering of huntingtin protein, a reduction of huntingtin aggregation in the brain of rats, the prevention of neuronal dysfunction, and an improvement in Huntington disease-like symptoms and median survival increase of 24%.5

“We expect that AMT-130 will be the first one-time administered AAV gene therapy to enter clinical testing for the treatment of Huntington disease, a devastating neurodegenerative disorder for which there is no approved disease-modifying treatment,” Kapusta added.

UniQure has stated that it is “very encouraged” by the reductions shown in mHTT, and that it believes “that knock-down of this magnitude has the potential to significantly alter the course of the disease.”

The planned phase 1/2 dose-escalating trial will assess the safety, tolerability, and efficacy of 1-time treatment with AMT-130 in patients with Huntington disease. UniQure has stated that it expects to begin dosing patients in the second half of 2019.

“AMT-130 also represents the first clinical-stage AAV-based therapy specifically designed to silence an abnormal gene in the brain with a single administration, and we believe our proprietary miQURE gene silencing platform has the potential to be applied to many other diseases, such as spinocerebellar ataxia type 3 (SCA3),” Kapusta said. “This achievement is a major milestone for uniQure’s research organization, who have dedicated years of effort with the hope we can one day offer treatment for the many patients waiting generations for an effective therapy.”

In October 2017, the FDA granted an Orphan Drug designation to AMT-130 in Huntington disease, and in January 2018, the European Medicines Agency granted it an Orphan Medicinal Product Designation (OMPD) for the same indication, making it the first investigational AAV-gene therapy in Huntington disease to receive such designation.


1. uniQure Announces FDA Clearance of Investigational New Drug Application for AMT-130 in Huntington’s Disease [press release]. Lexington, MA, and Amsterdam, the Netherlands: uniQure; Published January 22, 2019. globenewswire.com/news-release/2019/01/22/1703263/0/en/uniQure-Announces-FDA-Clearance-of-Investigational-New-Drug-Application-for-AMT-130-in-Huntington-s-Disease.html. Accessed January 22, 2019.

2. Samaranch L, Blits B, San Sabastian W, et al. MR-guided parenchymal delivery of adeno associated viral vector serotype 5 in non-human primate brain. Gene Ther. Published online March 2017. doi: 10.1038/gt.2017.14

3. Minniarikove J, Zanella I, Huseinovic A, et al. Design, characterization, and lead selection of therapeutic miRNAs targeting huntingtin for development of gene therapy for Huntington’s disease. Mol Ther-Nucl Acids. 2016;5:e297. doi: :10.1038/mtna.2016.7

4. uniQure has demonstrated preclinical proof-of-concept and has submitted an IND in Huntington's disease. UniQure website. uniqure.com/gene-therapy/huntingtons-disease.php. Accessed January 22, 2019.

5. Evers M. Establishing preclinical proof-of-concept of gene therapy for Huntington disease. Presented at: American Academy of Neurology 2018 Annual Meeting; Los Angeles, CA; April 21 to 27, 2018. uniqure.com/2018%20-%20American%20Academy%20of%20Neurology%20-%20Final.pdf. Accessed January 22, 2019.

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