Replies to post #57769 on Anavex Life Sciences Corp (AVXL)

[JB3729]

Donepezil has been shown to work on less than 50% of patients.

Additionally, from July, 2015 -

Kanak Kanti De - Let me see if I understand the science correctly. Is the primary function of Anavex 2-73 to correctly fold back misfolded protein? By stimulating the sigma-1r chaperone? Is there anything else that it does?

Christopher Missling - Correct, however, additionally targeting Sigma-1 receptor and muscarinic receptors, which ANAVEX 2-73 does, is believed to increase cellular plasticity and reduce oxidative stress, inflammation, abeta generation and tau hyperphosphorylation (Note: Please see the publications section on Anavex's website and the following publication for protein misfolding.)


KKD - And adding Aricept to it - that is to reduce the plaque that's already been built up by existing misfolded protein, correct?

CM - Reducing the abeta plaque is also a function of sigma-1 R. Adding Aricept (donepezil) is believed to increase acetylcholine, a messenger for memory and hence work synergistically with ANAVEX 2-73.

KKD - So, A2-73 may work in early stages of the disease, when plaque buildup isn't considerable, but needs a plaque reducing agent in more advanced stages?

CM- Possibly, however, preclinically ANAVEX 2-73 might be sufficient to also reduce abeta by itself. Hence, could be applicable both in MCI and mild-to-moderate Alzheimer's disease. The current Phase 2a is in mild-to-moderate Alzheimer's disease.

KKD - However, since there's no biomarker to properly identify onset of Alzheimer's disease, A2-73 as a monotherapy doesn't work right now, and you need donepezil?

CM - That answer will come from this current Phase 2a. However, preclinical evidence shows ANAVEX 2-73 works very well alone and might have a further boost in combination with donepezil.