uniQure Presents New Preclinical Data on AMT-130 in Huntington’s Disease at CHDI’s 12th Annual Huntington’s Disease The...
April 26 2017 - 7:00AM
-- One-time Administration of AMT-130
Demonstrates for the First Time Efficacy in Large Animal Model
uniQure N.V. (NASDAQ:QURE), a leading gene therapy company
advancing transformative therapies for patients with severe medical
needs, today presented new preclinical data on AMT-130, a gene
therapy candidate for the treatment of Huntington’s disease (HD),
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. AMT-130 consists of an AAV5
vector carrying a DNA cassette encoding artificial micro-RNA
(miHTT) that silences the huntingtin gene. 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.
“Using AAV vectors to deliver micro-RNAs
directly to the brain represents a highly innovative approach to
treating Huntington’s disease,” stated Prof. Motlik. “This study
demonstrated that a single administration of AAV5-miHTT resulted in
significant reductions in HTT mRNA in all regions of the brain
transduced by AMT-130, as well as in the cortex. Consistent with
the reduction in HTT mRNA, we also observed a clear dose-dependent
reduction in mutant huntingtin protein levels in the brain, with
similar trends in the cerebral spinal fluid. Taking into account
the similarities of CHDI’s proprietary transgenic pig model to the
human brain, these results provide additional data to support
moving forward with clinical trials of uniQure's promising gene
therapy for Huntington’s disease.”
Preclinical Data Findings
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.
“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,”
stated Pavlina Konstantinova, Ph.D., director of new therapeutic
target discovery at uniQure. “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 positive data
from this study, together with data from our previous studies in
rodent models showing strong reductions in huntingtin and
prevention of neuronal dysfunction, provide strong proof of concept
for AMT-130 as a potential groundbreaking treatment for patients
suffering from Huntington’s disease. We look forward to commencing
the toxicology study in non-human primates later this year, which
we expect to support an Investigational New Drug (IND) application
for AMT-130 in 2018.”
About Huntington’s
DiseaseHuntington’s disease is a rare, inherited
neurodegenerative disorder that leads to loss of muscle
coordination, behavioral abnormalities and cognitive decline,
resulting in complete physical and mental deterioration over a 12-
to 15-year period of time. The disease is caused by an autosomal
dominant mutation, a cytosine-adenine-guanine (CAG) expansion, in
the first exon of the huntingtin gene leading to a non-functional,
aggregation prone mutated protein. Despite the clear etiology,
there are no therapies available to treat the disease, delay onset
or slow progression of a patient's decline.
About uniQure uniQure is
delivering on the promise of gene therapy – single treatments with
potentially curative results. We are leveraging our modular and
validated technology platform to rapidly advance a pipeline of
proprietary and partnered gene therapies to treat patients with
hemophilia, Huntington’s disease and cardiovascular diseases.
www.uniQure.com
uniQure Forward-Looking
StatementsThis press release contains forward-looking
statements. All statements other than statements of historical fact
are forward-looking statements, which are often indicated by terms
such as "anticipate," "believe," "could," "estimate," "expect,"
"goal," "intend," "look forward to," "may," "plan," "potential,"
"predict," "project," "should," "will," "would" and similar
expressions. Forward-looking statements are based on management's
beliefs and assumptions and on information available to management
only as of the date of this press release. These forward-looking
statements include, but are not limited to, statements regarding
the winding down of our Glybera program, the development of our
other gene therapy product candidates, the success of our
collaborations and the risk of cessation, delay or lack of success
of any of our ongoing or planned clinical studies and/or
development of our product candidates. Our actual results could
differ materially from those anticipated in these forward-looking
statements for many reasons, including, without limitation, risks
associated with corporate reorganizations and strategic shifts,
collaboration arrangements, our and our collaborators’ clinical
development activities, regulatory oversight, product
commercialization and intellectual property claims, as well as the
risks, uncertainties and other factors described under the heading
"Risk Factors" in uniQure’s 2016 Annual Report on Form 10-K filed
on March 15, 2017. Given these risks, uncertainties and other
factors, you should not place undue reliance on these
forward-looking statements, and we assume no obligation to update
these forward-looking statements, even if new information becomes
available in the future.
uniQure Contacts:
Maria E. Cantor
Direct: 339-970-7536
Mobile: 617-680-9452
m.cantor@uniQure.com
Tom Malone
Direct: 339-970-7558
Mobile: 339-223-8541
t.malone@uniQure.com
Eva M. Mulder
Direct: +31 20 240 6103
Mobile: +31 6 52 33 15 79
e.mulder@uniQure.com
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