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Clinical Trials

Date: 2017-10-18

Type of information: Presentation of results at a congress

phase: preclinical

Announcement: presentation of results at the European Society of Gene and Cell Therapy (ESGCT) 25th Anniversary Congress

Company: Uniqure (The Netherlands)

Product: AMT-130 (adeno-associated viral vector serotype 5 encoding a microRNA targeted to human huntingtin gene)

Action mechanism:

  • gene therapy. AMT-130 consists of an AAV5 vector carrying a DNA cassette encoding artificial micro-RNA (miHTT) that silences the huntingtin gene.
  • The FDA  has granted  Orphan Drug Designation to AMT-130 (adeno-associated viral vector serotype 5 encoding a microRNA targeted to human huntingtin gene), for the treatment of Huntington's disease.

Disease: Huntington's Disease

Therapeutic area: Rare diseases - Genetic diseases - Neurodegenerative diseases

Country:

Trial details:

Latest news:

  • • On October 18, 2017, uniQure presented new preclinical data on AMT-130, its proprietary gene therapy candidate for the treatment of Huntington's disease , at the European Society of Gene and Cell Therapy (ESGCT) 25th Anniversary Congress in Berlin, Germany. Data from the study demonstrate that following administration of AMT-130 in Huntington's disease mouse models, significant improvements in both motor-coordination and survival were observed, as well as a dose-dependent, sustained reduction in huntingtin protein. The study on functional improvement and sustained huntingtin lowering was performed by members of uniQure's research department in collaboration with Charles River Discovery Research Services, Finland.
  • This study builds on previous data generated at uniQure, demonstrating a long-term significant suppression of mutant huntingtin protein, the cause of Huntington's disease, after a single administration of AMT-130 in the Q175 mouse model of Huntington's disease.
  • The current study was conducted in the R6/2 mouse model of Huntington's disease, which is characterized by early onset of motor symptoms and a much reduced life-span. A single administration of AMT-130 into the striatum was followed by a significant improvement of motor symptoms including improved coordination on the rotarod (a rotating cylinder to test coordination, physical condition and motor planning) as well as a significantly increased median survival from 120 to 149 days, compared with the control group (p = 0.0270). The data also demonstrate a significant reduction in expression of mutant huntingtin protein.
  • • On April 26, 2017, uniQure presented new preclinical data on AMT-130 at the 12th Annual CHDI HD Therapeutics Conference in Malta. Data from the study demonstrate 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. The proof-of-concept study was performed by uniQure in collaboration with Prof. Jan Motlik, Director of the Institute of Animal Physiology and Genetics in the Czech Republic and Ralf Reilmann, Founding Director of the George Huntington Institute in Germany.
  • Researchers in the study investigated the feasibility, efficacy and safety of AMT-130 in diseased animals with a larger brain size using a transgenic HD minipig model developed by Prof. Motlik and supported by the CHDI Foundation. AMT-130 was administered bilaterally into the striatum and thalamus of the minipigs using convection-enhanced, real-time MRI-guided delivery. Three months after treatment, widespread, dose-dependent distribution of the vector was observed throughout the minipig brain that corresponded strongly with the miHTT expression. Expression of mutant HTT mRNA was significantly reduced in all regions of the brain transduced by AMT-130 by 50% to 80%, as well in the cortex by up to 40%, compared with control. Researchers also observed a dose-dependent reduction in mutant huntingtin protein levels of more than 50% in the brain, as well as similar trends in cerebral spinal fluid. Both the surgical procedure and AAV5-miHTT treatment were well tolerated with no adverse events. The company now looks forward to commencing the toxicology study in non-human primates later this year, which uniQure expect to support an Investigational New Drug (IND) application for AMT-130 in 2018.

Is general: Yes