Anavex Life Sciences Corp (AVXL)

[Investor2014]

To my knowledge the closest we come to a description of MoA for A2-73 comes from the Goguadze N et al paper as referenced in this Anavex PR

Goguadze N et al presented preclinical data indicating that in addition to reducing oxidative stress, ANAVEX 2-73, ANAVEX 3-71 and ANAVEX 1-41 also demonstrated protective effects of the mitochondrial enzyme complexes I and IV during pathological conditions. The mitochondrial enzyme complex IV is directly involved in the synthesis of ATP, which provides energy within cells for metabolism. It is believed that energy production impairment and mitochondrial dysfunction play a role in the pathogenesis of neurodegenerative disorders and neurodevelopmental diseases.

“These new results provide converging evidence on mechanism of action as well as possible disease-modifying properties potentially by restoring homeostasis by means of the sigma-1 receptor agonists in our pipeline. This data also provides a foundation for our ongoing translational research efforts,” said Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex.

Both data sets described that Aß1-42 (amyloid beta) significantly impairs biological function in the respective animal models and the observed regain of function confirmed the protective potential of ANAVEX sigma-1 receptor agonists against amyloid beta -induced toxicity. The former presentation further reported that although that the transgenic McGill rats had a very late stage of Alzheimer’s disease-like pathology (13 months of age), treatment with ANAVEX 3-71 fully reversed cognitive deficits, reduced amyloid pathology and also significantly reduced inflammation. Furthermore, the sustained recovery in cognition and pathophysiology observed following a month-long washout phase in advanced pathology (19 months of age) strongly suggests true disease-modifying properties of ANAVEX 3-71.

I have not been able to find any references to Donepezil demonstrating protective effects of the mitochondrial enzyme complexes I and IV during pathological conditions.