Anavex Life Sciences Corp (AVXL)

[georgejjl]

Anavex 3-71

AF710B, an M1/sigma-1 receptor agonist with long-lasting disease-modifying properties in a transgenic rat model of Alzheimer's disease.
Hall H1, Iulita MF1, Gubert P1, Flores Aguilar L2, Ducatenzeiler A1, Fisher A3, Cuello AC4.
Author information
1
Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada.
2
Department of Anatomy and Cell Biology, McGill University, Montreal, Canada.
3
Department of Medicinal Chemistry, Israel Institute for Biological Research, Ness Ziona, Israel(§).
4
Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada; Department of Anatomy and Cell Biology, McGill University, Montreal, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, Canada. Electronic address: [e-mail].
Abstract
INTRODUCTION:
AF710B (aka ANAVEX 3-71) is a novel selective allosteric M1 muscarinic and sigma-1 receptor agonist. In 3×Tg-AD mice, AF710B attenuates cognitive deficits and decreases Alzheimer-like hallmarks. We now report on the long-lasting disease-modifying properties of AF710B in McGill-R-Thy1-APP transgenic (Tg) rats.

METHODS:
Chronic treatment with AF710B (10 µg/kg) was initiated in postplaque 13-month-old Tg rats. Drug or vehicle was administered orally daily for 4.5 months and interrupted 5 weeks before behavioral testing.

RESULTS:
AF710B long-term treatment reverted the cognitive deficits associated with advanced Alzheimer-like amyloid neuropathology in Tg rats. These effects were accompanied by reductions in amyloid pathology and markers of neuroinflammation and increases in amyloid cerebrospinal fluid clearance and levels of a synaptic marker. Importantly, these effects were maintained following a 5-week interruption of the treatment.

DISCUSSION:
With M1/sigma-1 activity and long-lasting disease-modifying properties at low dose, AF710B is a promising novel therapeutic agent for treating Alzheimer's disease.

https://www.ncbi.nlm.nih.gov/pubmed/29291374

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