Anavex Life Sciences Reports Newly Published Data on Alzheimer's Disease Research Demonstrate the Neuroprotective Features of...
November 21 2017 - 7:00AM
Anavex’ Sigma-1 Receptor Agonists Protect
Mitochondrial Function from Amyloid Toxicity and Absence of Sigma-1
Receptor Function Exacerbates Amyloid Toxicity
New data published in the current issue of the peer-reviewed
scientific journal Neurotoxicity Research1 confirm that
sigma-1 agonists, including multiple investigational compounds from
Anavex Life Sciences Corp. (“Anavex” or the “Company”)
(NASDAQ:AVXL), induce an anti-oxidant effect and protect
mitochondrial function in pathological central nervous system
conditions. In addition, another recent publication in the
peer-reviewed scientific journal, Behavioural Brain Research2,
confirms that the absence of sigma-1 receptor function exacerbates
amyloid toxicity and increases learning impairments in
pharmacologic and genetic mouse models of Alzheimer’s disease.
Lead author of both publications, Tangui Maurice, PhD, Professor
at INSERM Montpellier noted, “Both findings are consistent with the
concept that sigma-1 receptor activity seems to be essential for
cell survival under stress with the ability to counter the
different manifestations of Alzheimer’s disease and other
neurodegenerative pathologies.”
Mitochondrial dysfunction and oxidative damage are key factors
involved in the pathology of many neurodegenerative diseases.
Research shows that oxidative damage occurs in the brains of people
with Alzheimer’s disease prior to the onset of significant plaque
pathology3.
The Neurotoxicity Research publication provides further insight
on the mechanism of three Anavex sigma-1 receptor (S1R) agonists,
ANAVEX®2-73, ANAVEX®1-41, and ANAVEX®3-71, which are all being
studied in neurodegenerative diseases including Alzheimer’s disease
(AD), Parkinson’s disease (PD) and multiple sclerosis (MS). Since
S1R agonists are known to be potent neuroprotectants in preclinical
models, they might play a critical role in providing
neuroprotection for patients with AD and related disorders.
The second publication investigates how lack of S1R function
effects learning behavior and biochemical markers in a
pharmacologic and a genetic mouse model of AD. The transgenic mice,
bred to express human amyloid precursor protein (APP) carrying the
Swedish and Indiana mutations, APPSweInd (also known as the J20
line), were crossbred with S1R knockout (S1RKO) mice
(APPSweInd/S1RKO). Compared to APPSweInd or S1RKO mice,
APPSweInd/S1RKO exhibited an increased vulnerability to amyloid
toxicity and more pronounced deficits in both short and long term
memory. Furthermore, these deficits increased with age. Analyses of
oxidative stress and Bax expression levels in the hippocampus of
these animals also confirmed a higher level of toxicity in
APPSweInd mouse brains when S1R expression had been deleted. These
observations support the concept that S1R activity is a signal
amplifier for endogenous neuroprotection systems.
“These results seem to further validate sigma-1 receptor agonism
as a therapeutic target for the treatment of neurodegenerative
diseases,” stated Christopher U. Missling, PhD, President and Chief
Executive Officer of Anavex. “We continue our research on sigma-1
receptor agonists in a variety of central nervous system disorders,
with our lead candidate, ANAVEX®2-73, soon progressing to a
late-stage clinical trial for Alzheimer’s disease after positive
data in a Phase 2a study.”
1 Goguadze N, Zhuravliova E, Morin D, Mikeladze D, Maurice T,
Sigma-1 Receptor Agonists Induce Oxidative Stress in Mitochondria
and Enhance Complex I Activity in Physiological Condition but
Protect Against Pathological Oxidative Stress, Neurotox Res. 2017
Nov 10. doi: 10.1007/s12640-017-9838-2
2 Maurice T, Strehaiano M, Duhr F, Chevallier N, Amyloid
toxicity is enhanced after pharmacological or genetic invalidation
of the σ1 receptor, Behavioural Brain Research, Volume 339, 26
February 2018, Pages 1-10
3 Nunomura A, Perry G, Aliev G, Hirai K, Takeda A, Balraj EK,
Jones PK, Ghanbari H, Wataya T, Shimohama S, Chiba S, Atwood CS,
Petersen RB, Smith MA (2001) Oxidative damage is the earliest event
in Alzheimer disease. J Neuropathol Exp Neurol 60:759–767
About Anavex Life Sciences Corp.Anavex Life
Sciences Corp. (Nasdaq:AVXL) is a publicly traded biopharmaceutical
company dedicated to the development of differentiated therapeutics
for the treatment of neurodegenerative and neurodevelopmental
diseases including Alzheimer’s disease, other central nervous
system (CNS) diseases, pain and various types of cancer. Anavex’s
lead drug candidate, ANAVEX®2-73, recently completed a successful a
Phase 2a clinical trial for Alzheimer’s disease. ANAVEX®2-73 is an
orally available drug candidate that restores cellular homeostasis
by targeting sigma-1 and muscarinic receptors. Preclinical studies
demonstrated its potential to halt and/or reverse the course of
Alzheimer’s disease. It has also exhibited anticonvulsant,
anti-amnesic, neuroprotective and anti-depressant properties in
animal models, indicating its potential to treat additional CNS
disorders, including epilepsy. The Michael J. Fox Foundation for
Parkinson’s Research has awarded Anavex a research grant to develop
ANAVEX®2-73 for the treatment of Parkinson’s disease. The grant
fully funds a preclinical study, which could justify moving
ANAVEX®2-73 into a Parkinson’s disease clinical trial. ANAVEX®3-71,
also targeting sigma-1 and M1 muscarinic receptors, is a promising
preclinical drug candidate demonstrating disease modifications
against the major Alzheimer’s hallmarks in transgenic (3xTg-AD)
mice, including cognitive deficits, amyloid and tau pathologies,
and also with beneficial effects on neuroinflammation and
mitochondrial dysfunctions. Further information is available
at www.anavex.com. You can also connect with the company
on Twitter, Facebook and LinkedIn.
Forward-Looking StatementsStatements in this
press release that are not strictly historical in nature are
forward-looking statements. These statements are only predictions
based on current information and expectations and involve a number
of risks and uncertainties. Actual events or results may differ
materially from those projected in any of such statements due to
various factors, including the risks set forth in the Company’s
most recent Annual Report on Form 10-K filed with the SEC. Readers
are cautioned not to place undue reliance on these forward-looking
statements, which speak only as of the date hereof. All
forward-looking statements are qualified in their entirety by this
cautionary statement and Anavex Life Sciences Corp. undertakes no
obligation to revise or update this press release to reflect events
or circumstances after the date hereof.
For Further Information:Anavex Life Sciences
Corp. Research & Business Development Toll-free: 1-844-689-3939
Email: info@anavex.com
Investors & Media:Clayton Robertson The
Trout Group (646) 378-2900 crobertson@troutgroup.com
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