M1 muscarinic agonists and a multipotent activator of sigma1/M1 muscarinic receptors: Future therapeutics of Alzheimer’s disease (AD)
Confirms Sigma-1 Receptor Implicated in Targeting Depression, Anxiety, Epilepsy and Brain Injury after Ischemic Stroke
NEW YORK – June 30, 2014
Anavex Life Sciences Corp. (“Anavex” or the “Company”) (OTCQB: AVXL), a clinical-stage biopharmaceutical company developing novel drug candidates to treat Alzheimer’s disease, other diseases of the central nervous system (CNS) and various types of cancer, today announced that a paper in the current issue of the peer-reviewed scientific journal, Neurochemical Research, reveals for the first time that sigma-1 receptors (S1R) functionally downregulate certain proteins that play a major role in various pathophysiological conditions including depression, anxiety, epilepsy and brain injury following ischemic stroke.
“We are delighted to learn about these new findings that provide further evidence of potential additional significant therapeutic indications for the Anavex drug candidate family, which increase the expression of the sigma-1 receptor,” said Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex. “We look forward to continuing the preclinical work with our S1R agonist drug candidates in additional indications while we prepare for the Alzheimer’s disease clinical trial of ANAVEX PLUS, which is scheduled to commence in 2014.”
The study found that S1R downregulate the activity of ASIC1a (acid-sensing ion channel 1a) by interacting with the scaffolding protein AKAP150 (A-kinase anchoring protein 150). Increases in ASIC1a activity have been shown to contribute, for example, to neurodegeneration following ischemic stroke, generation and maintenance of epileptic seizures, and spinocerebellar ataxia 1 pathogenesis. Thus, the neuroprotective and therapeutic properties of S1R may in part be specifically mediated by the interactions of S1R with AKAP150 and downstream inhibition of ASIC1a.
These scaffold proteins (AKAP150) are a key part of post-synaptic complexes critical for synaptic transmission and help organize the macromolecular complex, which includes proteins such as NMDA receptors, AMPA receptors, voltage-gated calcium channels and beta-adrenergic receptors. Importantly, by coordinating the co-localization of these molecules, AKAP150 influences learning and memory. In addition, displacement of AKAP150 from dendritic spines following large elevations in cell calcium has been implicated in excitotoxicity, the pathological process through which nerve cells are damaged and killed by excessive levels of neurotransmitters. The study indicates that S1R reside in a critical juncture that permits protection of neurons from injury by preventing calcium overload near AKAP150 complexes, which may in part help to explain the therapeutic efficacy of S1R agonists like ANAVEX PLUS and ANAVEX 2-73 in disorders such as Alzheimer’s disease. In addition, the S1R inhibition of ASIC1a itself is now of great interest for other clinical indications.
The lead author of the study, Dr. Javier Cuevas, PhD, professor of Molecular Pharmacology and Physiology at the University of South Florida College of Medicine, commented: “Our laboratory has shown that S1R affect a variety of ion channels that cause pronounced elevations in intracellular calcium, and that by decreasing the activity of these channels, S1R help prevent cell death.” Dr. Cuevas continues, “The observation that S1R interact with AKAP150 likely explains the broad effects of S1R, which uniquely permits these receptors to be effective therapeutic targets in a variety of neurodegenerative diseases.”
The report, entitled “Sigma-1 Receptor Inhibition of ASIC1a Channels is Dependent on a Pertussis Toxin-Sensitive G-Protein and an AKAP150/Calcineurin Complex,” was authored by Dr. Javier Cuevas and colleagues from the Department of Molecular Pharmacology and Physiology at the University of South Florida College of Medicine.
About Anavex Life Sciences Corp.
Anavex Life Sciences Corp. (www.anavex.com) is a clinical-stage biopharmaceutical company engaged in the development of novel drug candidates to treat Alzheimer’s disease, other CNS diseases and various types of cancer. ANAVEX 2-73, an orally available drug candidate developed to treat Alzheimer’s disease through potential disease modification, has undergone an initial Phase 1 human clinical trial and was well tolerated in doses up to 55mg. Results from preclinical studies indicate that ANAVEX 2-73 demonstrates anti-amnesic and neuroprotective properties. A highly encouraging synergistic effect has also been observed between ANAVEX 2-73 and donepezil (Aricept®). The combined therapeutic, called ANAVEX PLUS, produced up to 80% greater reversal of memory loss in Alzheimer’s disease models versus when the drugs were used individually. Anavex is a publicly traded corporation quoted as AVXL.
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.
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