Gene Therapy:

Huntington's Disease

uniQure's has demonstrated preclinical proof-of-concept and initiated IND-enabling studies 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 over a 12- to 15-year period. HD is caused by the expansion of CAG trinucleotide in exon 1 of a multifunctional gene coding for protein called huntingtin.

Huntington’s disease represents a large, high-unmet medical need. There are an estimated 28,000 HD patients in the U.S. and approximately 35,000 Huntington’s disease patients in the EU.  Despite the clear etiology of the disease, there are no therapies available to treat HD, delay its onset, or slow the progression of a patient's decline.

Our product candidate AMT-130 consists of an AAV5 vector carrying an artificial micro-RNA specifically tailored to silence the huntingtin gene. The therapeutic goal is to inhibit the production of the mutant protein.  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.

uniQure achieved preclinical proof-of-concept in early 2016 with the publication of data demonstrating the potential of a one-time administration of AAV5-delivered gene therapy to successfully silence the huntingtin gene (view publication).  In April 2017, uniQure published two additional preclinical studies that support moving forward with clinical trials of this promising gene therapy.  This includes data demonstrating widespread transduction in the central nervous system following direct injection of uniQure's AAV5 vector in a large animal model (view publication).  Data from a second study demonstrated widespread and effective AAV5 vector distribution and extensive silencing of the human mutant huntingtin gene (HTT) in minipigs, among the largest HD animal models available for testing (view poster presentation).  This study is an important step in our Huntington’s disease gene therapy program, demonstrating for the first time in a large animal model that AAV5 can be used safely and effectively to deliver micro-RNAs to silence mutant huntingtin. 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.  

In October 2017, the U.S. Food and Drug Administration granted orphan drug designation for AMT-130 in Huntington’s disease. In January 2018, AMT-130 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.

We expect to file an Investigational New Drug (IND) application and to enter clinical development for AMT-130 in 2018.