New preclinical data establishes ANAVEX®2-73 as a modulator of autophagy through Sigma-1 receptor activation, possibly needed for the prevention and treatment of neurodegenerative conditions including Alzheimer’s disease, Parkinson’s disease and ALS
NEW YORK, March 04, 2019 (GLOBE NEWSWIRE) -- Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative and neurodevelopmental diseases including Alzheimer’s disease, Parkinson’s disease, Rett syndrome and other central nervous system (CNS) diseases, today announced the publication by an independent scientific group of new preclinical data for ANAVEX®2-73, an orally available investigational therapy that restores cellular homeostasis by targeting the sigma-1 receptor (Sig-1R) and muscarinic receptors. The drug has completed a Phase 2a clinical trial and is currently being studied in a Phase 2b/3 study for the treatment of early Alzheimer’s disease and a Phase 2 study for Parkinson’s disease dementia.
The current findings show for the first time that activation of Sig-1R with ANAVEX®2-73 leads to the prominent induction of the autophagy “cellular recycling” process and enhanced protein clearance in cells. The study, led by Christian Behl et. al. of the University Medical Center at Johannes Gutenberg University, in Mainz, Germany, has been published in the peer-reviewed journal, Cells (link).
“These results show that activating the sigma-1 receptor (Sig-1R) with ANAVEX®2-73 can selectively induce the autophagy process and increase protein homeostasis in both in vitro and in vivo models,” said Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex. “The ability to identify key molecular functions in age-related disease is central to developing new therapeutic strategies that target these mechanisms and ultimately provide clinical impact by preventing or treating disease.”
Autophagy is a cellular process that cleans cells of defective proteins and is part of a set of mechanisms that participate in proteostasis, or the balance of the protein network. Loss of proteostasis and dysfunction of the autophagy process, has been closely linked to the pathogenesis of human neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and ALS1.
“There is a great amount of data linking dysfunction and malfunction of autophagy to neurodegenerative disease and, consistent with its role in proteostasis, to the accumulation of protein aggregates. Thus, the modulation of autophagy has become one key pharmacological target in neurodegeneration,” the researchers reported. “In fact, there are multiple overlaps of autophagy and pathogenesis pathways in Alzheimer’s disease, Parkinson’s disease, and ALS. Recently different alternative views and new pharmacological targets towards Alzheimer’s prevention and treatment are evolving and include a strong focus on the autophagy process.”
The Cells paper also noted that this is the first report to show that Sig-1R activation enhances the autophagic flux in human cells and in C. elegans with positive effects on proteostasis in vitro and in vivo, an important concept towards the stabilization of neuronal survival and function that may help to prevent age-associated neurodegeneration.
The paper entitled, “Sigma-1 Receptor Activation Induces Autophagy and Increases Proteostasis Capacity In Vitro and In Vivo,” can be found online on the Cells website.
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, Parkinson’s disease, Rett syndrome and other central nervous system (CNS) diseases, pain and various types of cancer. Anavex’s lead drug candidate, ANAVEX®2-73, recently completed a successful 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. 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. ANAVEX®3-71, which targets sigma-1 and M1 muscarinic receptors, is a promising preclinical 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 neuroinflammation and mitochondrial dysfunction. Further information is available at www.anavex.com. You can also connect with the company on Twitter, Facebook and LinkedIn.
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1 Klaips, C.L.; Jayaraj, G.G.; Hartl, F.U. Pathways of cellular proteostasis in aging and disease. J. Cell Biol. 2018, 217, 51–63.; Ramesh N, Pandey UB. Autophagy Dysregulation in ALS: When Protein Aggregates Get Out of Hand. Front Mol Neurosci. 2017;10:263.