Anavex was selected to present its latest results with Anavex 1-41 at Neuroscience 2008, the 38th annual meeting of the Society for Neuroscience, which took place on 15-19 November 2008 in Washington.
In a scientific poster abstract, Anavex detailed the neuroprotective potential of Anavex 1-41, evidenced by its ability to block the manifestation of the earliest toxic effects in a validated mouse model of Alzheimer's disease.
Currently in the late pre-clinical stage, Anavex 1-41 has shown synergistic potential for anti-amnesic and neuroprotective efficacy at low doses.
Anavex said this is the first time these results have been attained by any pharmacological agent in an Alzheimer's mouse model involving the injection of the amyloid-beta (25-35) peptide.
The earliest toxic effects of Alzheimer's disease mouse models were measured by the expression of the caspase-12 marker.
Caspase 12 is a recently discovered enzyme that indicates these early toxic effects.
Non-transgenic Alzheimer's mouse models are created by injecting amyloid-beta peptide into mouse brains to bring on histological and biochemical changes, oxidative stress and learning deficits.
The neuroprotective potential of Anavex 1-41 is hypothesised to act by the compound's ability to modulate sigma receptors which regulate calcium mobilisation in neuronal cells.
Calcium is regulated through the Inositol Triphosphate receptors 'IP3R' and the sarcoendoplasmic reticulum 'Ca2+/ATPase' pump.
The major effect of Anavex 1-41 occurs at the membrane of neuronal cells, in the endoplasmic reticulum (ER).
The novel profile of Anavex 1-41, which is a mixed sigma-1, muscarinic and sodium-channel candidate drug, accounts for its ability to fight ER stress and thereby prevent apoptosis of the neuronal cells.
This neuronal apoptosis is the prominent pathophysiological effect of brain degeneration in Alzheimer's disease.
The neuroprotective effects of Anavex 1-41 were assessed in the hippocampus, the area of the brain that regulates learning, emotion and memory and which is highly implicated in Alzheimer's disease.
As recently discovered in pre-clinical testing, through its sigma-1 activity, Anavex 1-41 targets neuron structures (ER, mitochondria), as well as disturbed biochemical pathways and channels (UPR,IP3R,Bcl-2,apoptosis).
Organisations involved in sigma receptor research have determined that these are crucial factors in Alzheimer's disease and in many other neurodegenerative diseases.
The company expects to complete pre-clinical trials on Anavex 1-41 in early 2009.
