BRISBANE, Calif., March 29, 2019 /PRNewswire/
-- Sangamo Therapeutics, Inc. (NASDAQ: SGMO), a genomic
medicine company, presented new preclinical data demonstrating
significant (>80%) reduction of tau expression in the nonhuman
primate brain following administration of zinc finger protein
transcription factors (ZFP-TFs). Tau pathology is strongly linked
to the progression of several neurodegenerative diseases, called
tauopathies, including Alzheimer's disease. The data, reported in a
podium presentation at the 14th International Conference
on Alzheimer's & Parkinson's Diseases (ADPD) held in
Lisbon, Portugal, described the
effects of tau-targeted ZFP-TFs delivered with adeno-associated
viruses (AAVs) in the mouse and nonhuman primate (NHP)
brain.
Sangamo's ZFP-TF technology acts at the DNA level to selectively
repress or activate the expression of specific genes to achieve a
desired therapeutic effect. Gene regulation differs from other
genome editing approaches as it is designed to enable precise,
robust, and long-term repression of a selected gene following a
single administration of AAV and does not cut or modify the target
DNA.
Tauopathies are characterized by the accumulation of toxic tau
protein in the brain that leads to widespread neuronal dysfunction
and loss. Reducing the total amount of tau expressed within neurons
has been shown to provide benefit in animal models of
tauopathies.
"There are currently no disease modifying therapies approved for
the treatment of tauopathies. While many tau-targeted approaches
are currently being explored, a key challenge has been the
incomplete understanding of the toxic tau proteins that drive
disease progression, which are complex and vary between
tauopathies. Sangamo's proprietary ZFP-TF gene regulation
technology provides a differentiated approach to this problem by
focusing on lowering all forms of tau at the DNA level and has the
potential to provide significant therapeutic benefits for tauopathy
patients," said Adrian Woolfson,
BM., B.Ch., Ph.D., Executive Vice President of Research and
Development at Sangamo. "These results also demonstrate the high
degree of precision, efficiency and specificity of our zinc finger
protein transcription factor platform and demonstrate how gene
specific transcriptional regulation may play a key role in the
future treatment of central nervous system diseases."
The goal of the preclinical studies presented at ADPD was to
assess the pharmacology of tau gene repression in the mouse and NHP
brain. AAV vectors were used to deliver tau-targeted ZFP-TFs in
vitro to neurons and in vivo to vulnerable brain regions
that are impacted by tauopathies. The data demonstrate that ZFP-TFs
selectively reduced mouse and human tau by up to 98% in
vitro in both primary mouse and induced pluripotent stem
cell-derived human neurons. Intrahippocampal ZFP-TF delivery to
adult mice resulted in more than 80% tau reduction, and intravenous
ZFP-TF administration reduced tau levels by 50-70% across the
entire mouse brain. ZFP-TF expression and mouse tau reduction were
sustained for at least six months following a single
administration. Furthermore, in APP/PS1 mice, tau-targeted ZFP-TFs
reduced dystrophic neurites by approximately 50% across the
cerebral cortex.
AAV ZFP-TFs targeting tau were administered to the adult NHP
hippocampus using real-time MRI-guided stereotaxic infusion. ZFP-TF
treatment resulted in more than 80% lowering of tau in the
hippocampus and entorhinal cortex, and transgene expression levels
were strongly correlated with tau reduction. The treatment was well
tolerated for the duration of the study. Together these data from
mice and NHPs highlight the potential for a single administration
of ZFP-TF to lower tau as a treatment for tauopathies, including
Alzheimer's disease.
Preclinical development of tau-targeted ZFP-TFs is ongoing, and
Sangamo plans to present additional data at a future scientific
meeting.
Sangamo is also developing potential ZFP-TF gene therapies for
amyotrophic lateral sclerosis (ALS) and Huntington's disease, which
are linked to mutations in the C9ORF72 gene and CAG repeat
expansion in the HTT gene respectively. The ALS research is being
performed in collaboration with Pfizer, while the Huntington's
disease research is being performed in collaboration with Takeda.
About Sangamo Therapeutics
Sangamo
Therapeutics, Inc. is focused on translating ground-breaking
science into genomic medicines with the potential to transform
patients' lives using the Company's platform technologies in genome
editing, gene therapy, gene regulation and cell therapy. For more
information about Sangamo, visit www.sangamo.com.
Forward-Looking Statements
This press release
contains forward-looking statements based on Sangamo's current
expectations. These forward-looking statements include, without
limitation, statements relating to the potential therapeutic
applications for Sangamo's ZFP-TF platform technology, the ability
of ZFP-TFs to potentially lower all forms of tau levels at the DNA
level and provide significant therapeutic benefits to treat
tauopathies, including Alzheimer's disease and other central
nervous system diseases, Sangamo's plans for the ongoing
development of tau-targeted ZFP-TFs and plans to present additional
data, and other statements that are not historical fact. These
statements are not guarantees of future performance and are subject
to certain risks, uncertainties and assumptions that are difficult
to predict. Factors that could cause actual results to differ
include, but are not limited to, risks and uncertainties related to
early preclinical data, including the risk that the early
preclinical data may not warrant regulatory approvals to conduct
human clinical trials, and may not be representative of results of
any such human clinical trials; that ZFN-TFs may not produce any
beneficial therapeutic effect in humans; Sangamo's reliance on
partners and other third-parties to further develop its technology;
Sangamo's ability to develop commercially viable products; and the
potential for technological developments by Sangamo's competitors
that will be better than Sangamo's ZFN-TF technology. These risks
and uncertainties and other risks are described more fully in
Sangamo's Annual Report on Form 10-K for the year
ended December 31, 2018 as filed with the Securities
and Exchange Commission. Forward-looking statements contained in
this press release are made as of this date, and Sangamo undertakes
no duty to update such information except as required under
applicable law.
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SOURCE Sangamo Therapeutics, Inc.