Anavex’ Sigma-1 Receptor Agonists Protect Mitochondrial Function from Amyloid Toxicity and Absence of
Sigma-1 Receptor Function Exacerbates Amyloid Toxicity
NEW YORK, Nov. 21, 2017 (GLOBE NEWSWIRE) -- 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 Statements
Statements 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
