Anavex Life Sciences Reports New Publication in Medical Journal Highlighting the Established Precise Autophagy Mechanism with Blarcamesine
NEW YORK, Aug. 26, 2025 (GLOBE NEWSWIRE) -- Anavex Life Sciences Corp. ("Anavex" or the "Company") (NASDAQ:AVXL), a clinical-stage biopharmaceutical company focused on developing innovative treatments for Alzheimer's disease, Parkinson's disease, schizophrenia, neurodevelopmental, neurodegenerative, and rare diseases, including Rett syndrome, and other central nervous system (CNS) disorders, today reported a peer-reviewed publication in the journal iScience, ascertaining the precise autophagy mechanism of sigmar-1 receptor (S1R/SIGMAR1) through blarcamesine activation, titled "Conserved LIR-specific interaction of Sigma-1 receptor and GABARAP."1
The mechanistic confirmation that blarcamesine restores impaired autophagy through S1R/SIGMAR1 activation by acting upstream of amyloid and tau pathologies at the molecular level was previously established both in vitro and in vivo. Specifically, studies demonstrated enhanced autophagic flux in human cells and in C. elegans as well as increased proteostasis capacity, ultimately ameliorating paralysis caused by protein aggregation in C. elegans. In that study the widely published reference S1R agonist PRE-084 demonstrated the same autophagy restorative effect as established with blarcamesine, strengthening the rationale that the activation is analogous in both drugs.2
This new publication confirms with additional biochemical data in more detail the autophagy restoration mechanism of S1R activation with blarcamesine. The specific S1R-localized motif responsible for physiologically relevant interactions with autophagy proteins—promoting autophagosome biogenesis, autophagic cargo reception, and lysosome fusion—was confirmed and modulated by blarcamesine.
"We are excited about the ability to confirm the more precise mechanism of autophagy restoration through oral blarcamesine, which has demonstrated very persuasive clinical data in early Alzheimer's disease," said Juan Carlos Lopez-Talavera, MD, PhD, Head of Research and Development of Anavex. "The interaction reported in this study could represent a missing biochemical link in autophagy modulation by S1R."
S1R/SIGMAR1 has emerged as one of the prominent targets in treating neurodegeneration. It promotes autophagy and results in the degradation of amyloid-beta precursor protein (APP), thereby normalizing Aβ production.3 S1R/SIGMAR1 activation promotes neurogenesis, reduces reactive oxygen species (ROS) formation, suppresses neuroinflammation, and ameliorates Aβ toxicity. S1R/SIGMAR1 is also involved in maintaining endoplasmic reticulum (ER) function and regulating calcium.4 Data suggest that activation of S1R/SIGMAR1 results in the restoration of homeostatic function within the body and is pivotal to restoring neural cell balance and promoting neuroplasticity.5
Recent studies with Anavex compounds, blarcamesine (ANAVEX®2-73) and ANAVEX®3-71 show that S1R/SIGMAR1 activation also involves mitochondrial performance, an intricate phenomenon that provides energy for cellular functions.6 S1R/SIGMAR1 agonists, including blarcamesine (ANAVEX®2-73) and ANAVEX®3-71, have been reported to reduce toxic Aβ, tau, and neuroinflammation.7
"This independent paper elucidates more clearly the blarcamesine-activated S1R/SIGMAR1 direct interference with the autophagic process, by functioning as direct autophagy receptor and hence explaining the relevance of restoring impaired autophagy as early event, preceding amyloid-beta and tau as a compensatory mechanism to chronic CNS diseases, especially Alzheimer's disease," said Christopher U Missling, PhD, President and Chief Executive Officer of Anavex.
The paper can be accessed online at: https://www.sciencedirect.com/science/article/pii/S2589004225015482.
This release discusses investigational uses of an agent in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that any investigational uses of such product will successfully complete clinical development or gain health authority approval.
About Anavex Life Sciences Corp.
Anavex Life Sciences Corp. (NASDAQ:AVXL) is a publicly traded biopharmaceutical company dedicated to the development of novel therapeutics for the treatment of neurodegenerative, neurodevelopmental, and neuropsychiatric disorders, including Alzheimer's disease, Parkinson's disease, schizophrenia, Rett syndrome, and other central nervous system (CNS) diseases, pain, and various types of cancer. Anavex's lead drug candidate, ANAVEX®2-73 (blarcamesine), has successfully completed a Phase 2a and a Phase 2b/3 clinical trial for Alzheimer's disease, a Phase 2 proof-of-concept study in Parkinson's disease dementia, and both a Phase 2 and a Phase 3 study in adult patients and one Phase 2/3 study in pediatric patients with Rett syndrome. ANAVEX®2-73 is an orally available drug candidate designed to restore cellular homeostasis by targeting SIGMAR1 and muscarinic receptors. Preclinical studies demonstrated its potential to halt and/or reverse the course of Alzheimer's disease. ANAVEX®2-73 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 previously awarded Anavex a research grant, which fully funded a preclinical study to develop ANAVEX®2-73 for the treatment of Parkinson's disease. We believe that ANAVEX®3-71, which targets SIGMAR1 and M1 muscarinic receptors, is a promising clinical stage drug candidate demonstrating disease-modifying activity against the major hallmarks of Alzheimer's disease in transgenic (3xTg-AD) mice, including cognitive deficits, amyloid, and tau pathologies. In preclinical trials, ANAVEX®3-71 has shown beneficial effects on mitochondrial dysfunction and neuroinflammation. Further information is available at www.anavex.com. You can also connect with the Company on Twitter, Facebook, Instagram, and LinkedIn.
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1 Baeken et al. "Conserved LIR-specific interaction of Sigma-1 receptor and GABARAP." iScience Volume 28, Issue 9, 2025, 113287.
2 Christ, M G et al. "Sigma-1 Receptor Activation Induces Autophagy and Increases Proteostasis Capacity In Vitro and In Vivo." Cells vol. 8,3 211. 2 Mar. 2019.
3 Jaeger PA, Pickford F, Sun C-H, et al. Regulation of amyloid precursor protein processing by the Beclin 1 complex. PloS one. 2010;5(6):e11102.
4 Nguyen L, Lucke-Wold BP, Mookerjee SA, et al. Role of sigma-1 receptors in neurodegenerative diseases. Journal of pharmacological sciences. 2015;127(1):17-29; Moriguchi S, Shinoda Y, Yamamoto Y, et al. Stimulation of the sigma-1 receptor by DHEA enhances synaptic efficacy and neurogenesis in the hippocampal dentate gyrus of olfactory bulbectomized mice. PloS one. 2013;8(4):e60863-e60863; Rosen DA, Seki SM, Fernández-Castañeda A, et al. Modulation of the sigma-1 receptor–IRE1 pathway is beneficial in preclinical models of inflammation and sepsis. Science Translational Medicine. 2019;11(478):eaau5266; Maurice T, Volle J-N, Strehaiano M, et al. Neuroprotection in non-transgenic and transgenic mouse models of Alzheimer's disease by positive modulation of σ1 receptors. Pharmacological research. 2019;144:315-330.
5 Advances in Experimental Medicine and Biology Volume 964 (2017) Sigma Receptors: Their Role in Disease and as Therapeutic Targets.
6 Goguadze, N., Zhuravliova, E., Morin, D., Mikeladze, D., & Maurice, T. (2019). Sigma-1 Receptor Agonists Induce Oxidative Stress in Mitochondria and Enhance Complex I Activity in Physiological Condition but Protect Against Pathological Oxidative Stress. Neurotoxicity research, 35(1), 1–18.
7 Lahmy V, Meunier J, Malmström S, et al. Blockade of Tau hyperphosphorylation and Aβ 1–42 generation by the aminotetrahydrofuran derivative ANAVEX2-73, a mixed muscarinic and σ 1 receptor agonist, in a nontransgenic mouse model of Alzheimer's disease. Neuropsychopharmacology. 2013;38(9):1706-1706; Fisher A, Bezprozvanny I, Wu L, Ryskamp DA, Bar-Ner N, Natan N, Brandeis R, Elkon H, Nahum V, Gershonov E, LaFerla FM, Medeiros R. AF710B, a Novel M1/σ1 Agonist with Therapeutic Efficacy in Animal Models of Alzheimer's Disease. Neurodegener Dis. 2016;16(1-2):95-110.
