Anavex Life Sciences Reports New Publication in Medical Journal Highlighting the Established Precise Autophagy Mechanism with Blarcamesine
Anavex Life Sciences (NASDAQ:AVXL) announced a new peer-reviewed publication in iScience journal that details the precise autophagy mechanism of their drug blarcamesine. The study confirms how blarcamesine restores impaired autophagy through S1R/SIGMAR1 activation, acting upstream of amyloid and tau pathologies at the molecular level.
The research validates the specific S1R-localized motif's role in promoting autophagosome biogenesis, autophagic cargo reception, and lysosome fusion. This mechanism is particularly significant for treating neurodegenerative conditions, as S1R/SIGMAR1 activation helps reduce toxic Aβ, tau, and neuroinflammation while promoting neurogenesis and regulating cellular functions.
Anavex Life Sciences (NASDAQ:AVXL) ha pubblicato un nuovo articolo peer-reviewed su iScience che descrive nel dettaglio il preciso meccanismo di autofagia del loro farmaco blarcamesine. Lo studio conferma come blarcamesine ripristini l’autofagia compromessa tramite l’attivazione di S1R/SIGMAR1, agendo a monte delle patologie da amiloide e tau a livello molecolare.
La ricerca convalida il ruolo di un motivo localizzato su S1R nel favorire la biogenesi degli autofagosomi, il riconoscimento del materiale destinato all’autofagia e la fusione con i lisosomi. Questo meccanismo è particolarmente rilevante per il trattamento delle malattie neurodegenerative, poiché l’attivazione di S1R/SIGMAR1 contribuisce a ridurre le forme tossiche di Aβ, tau e l’infiammazione neurogena, oltre a promuovere la neurogenesi e regolare funzioni cellulari.
Anavex Life Sciences (NASDAQ:AVXL) anunció una nueva publicación revisada por pares en la revista iScience que detalla el mecanismo preciso de autofagia de su fármaco blarcamesina. El estudio confirma cómo blarcamesina restaura la autofagia dañada mediante la activación de S1R/SIGMAR1, actuando río arriba de las patologías por amiloide y tau a nivel molecular.
La investigación valida el papel de un motivo localizado en S1R para promover la biogénesis de autofagosomas, la recepción de la carga autofágica y la fusión con lisosomas. Este mecanismo resulta especialmente relevante para tratar afecciones neurodegenerativas, ya que la activación de S1R/SIGMAR1 ayuda a reducir las formas tóxicas de Aβ, tau y la neuroinflamación, además de promover la neurogénesis y regular funciones celulares.
Anavex Life Sciences (NASDAQ:AVXL)는 iScience 저널에 동료 심사(peer-reviewed)를 거친 새 논문을 발표했으며, 이 논문은 그들의 약물 블라르카메신(blarcamesine)의 정확한 자가포식(autophagy) 메커니즘을 자세히 설명합니다. 연구는 블라르카메신이 S1R/SIGMAR1 활성화를 통해 손상된 자가포식을 회복시키며 분자 수준에서 아밀로이드 및 타우 병리보다 상류에서 작용함을 확인합니다.
연구는 S1R에 국한된 특정 모티프가 오토파고좀의 생성, 자가포식 표적의 인식 및 리소좀과의 융합을 촉진하는 역할을 한다는 것을 검증했습니다. 이 메커니즘은 S1R/SIGMAR1 활성화가 독성 Aβ, 타우 및 신경염증을 감소시키고 신경 발생을 촉진하며 세포 기능을 조절하기 때문에 신경퇴행성 질환 치료에 특히 중요합니다.
Anavex Life Sciences (NASDAQ:AVXL) a publié un nouvel article évalué par des pairs dans la revue iScience qui détaille le mécanisme précis d’autophagie de son médicament blarcamesine. L’étude confirme que la blarcamesine restaure l’autophagie altérée via l’activation de S1R/SIGMAR1, agissant en amont des pathologies d’amyloïde et de tau au niveau moléculaire.
La recherche valide le rôle d’un motif localisé sur S1R dans la promotion de la biogenèse des autophagosomes, la réception des cargos autophagiques et la fusion lysosomale. Ce mécanisme est particulièrement important pour le traitement des maladies neurodégénératives, car l’activation de S1R/SIGMAR1 aide à réduire les formes toxiques d’Aβ, tau et l’inflammation neuro, tout en favorisant la neurogenèse et en régulant les fonctions cellulaires.
Anavex Life Sciences (NASDAQ:AVXL) hat eine neue, peer-reviewed Veröffentlichung in der Zeitschrift iScience bekanntgegeben, die den genauen Autophagie-Mechanismus ihres Wirkstoffs blarcamesine beschreibt. Die Studie bestätigt, wie blarcamesine gestörte Autophagie durch Aktivierung von S1R/SIGMAR1 wiederherstellt und dabei molekular oberhalb der Amyloid- und Tau-Pathologien wirkt.
Die Forschung validiert die Rolle eines S1R-lokalisierten Motivs bei der Förderung der Autophagosomen-Biogenese, der Aufnahme autophagischer Fracht und der Fusion mit Lysosomen. Dieser Mechanismus ist besonders relevant für die Behandlung neurodegenerativer Erkrankungen, da die Aktivierung von S1R/SIGMAR1 toxisches Aβ, Tau und Neuroinflammation reduziert sowie Neurogenese fördert und zelluläre Funktionen reguliert.
- Publication in peer-reviewed journal confirms precise mechanism of action for blarcamesine
- Research validates blarcamesine's role in restoring impaired autophagy, a key process in treating neurodegenerative diseases
- Study strengthens scientific understanding of how blarcamesine may treat Alzheimer's disease
- None.
Insights
Anavex's publication confirms blarcamesine's mechanism in restoring autophagy through S1R activation, strengthening its scientific foundation for Alzheimer's treatment.
This publication in iScience represents an important scientific validation for Anavex's therapeutic approach. The paper confirms the precise mechanism by which blarcamesine activates the sigma-1 receptor (S1R/SIGMAR1) to restore impaired autophagy - the cellular process responsible for clearing protein aggregates and damaged components. The research identifies a specific S1R-localized motif that interacts with autophagy proteins, promoting autophagosome biogenesis and lysosome fusion, which was modulated by blarcamesine.
What makes this significant is that autophagy dysfunction occurs upstream of amyloid and tau pathologies in Alzheimer's disease, suggesting blarcamesine addresses a root cause rather than just symptoms. The paper confirms previous findings that showed enhanced autophagic flux in human cells and C. elegans models, with improved proteostasis capacity that ameliorated paralysis caused by protein aggregation.
The mechanism aligns with the current understanding that S1R activation promotes neurogenesis, reduces oxidative stress, suppresses neuroinflammation, and ameliorates amyloid-beta toxicity. Importantly, the publication indicates blarcamesine's S1R-mediated autophagy restoration represents a compensatory mechanism for chronic CNS diseases, particularly Alzheimer's. This provides stronger scientific rationale for blarcamesine's development in neurodegenerative conditions where protein misfolding and aggregation are key pathological features.
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.
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:
Andrew J. Barwicki
Investor Relations
Tel: 516-662-9461
Email: andrew@barwicki.com
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.
FAQ
What did the new Anavex (AVXL) publication reveal about blarcamesine?
How does blarcamesine (ANAVEX 2-73) work in treating neurodegenerative diseases?
What is the significance of the S1R/SIGMAR1 mechanism for Anavex's drug development?
What are the potential therapeutic applications of blarcamesine based on this research?
Where was the new Anavex (AVXL) research published?
