Anavex Life Sciences Corp (AVXL)

[XenaLives]

Anavex has four upcoming presentations March 30-April 1 at the 13th Annual Conference on Alzheimer's and Parkinson's Diseases.


Thursday, March 30; 14:45-16:45: HALL A
AD/PDTM 2017 FORUM ON TRANSLATIONAL RESEARCH IN DRUG DISCOVERY FOR AD: A PLETHORA OF TARGETS: WHICH IS THE BEST, IS THERE "A BEST ONE"?

AD/PDTM 2017 FORUM ON TRANSLATIONAL RESEARCH IN DRUG DISCOVERY FOR AD: A PLETHORA OF TARGETS: WHICH IS THE BEST, IS THERE "A BEST ONE"?

Thursday, March 30; 14:45-16:45: HALL A

Moderator: Ezio Giacobini, University of Geneva Medical School Hospitals, Switzerland and Bengt Winblad, Karolinska Institute, Sweden

Susan Catalano, Founder & CSO, Cognition Therapeutics Inc, USA: DIRECT DISPLACEMENT OF Aß OLIGOMERS FOR EFFFECTIVE ALZHEIMER'S DIEASE MODIFICATION: CLINICAL EXPERIENCE WITH CT1812

David Elmaleh, Scientific Founder and Chairman?, AZ Therapeutics, USA

Teiji Kimura, Chief Discovery Officer, Eisai, Japan: COMBINATION THERAPY ERA WILL EMERGE FOR ALZHEIMER'S DISEASE MODIFICATION IN NEAR FUTURE. CAN BIOMARKERS SUGGEST THE BEST OPTION TO HETEROGENEOUS PATIENTS?

Christopher U. Missling, President & CEO, Anavex Life Sciences Corp., USA: RESTORING CELLULAR HOMEOSTASIS: DEVELOPING TARGETED THERAPIES FOR THE TREATMENT OF NEURODEVELOPMENTAL AND NEURODEGENERATIVE DISEASES UNDER THE PRECISION MEDICINE PARADIGM

??Martin Tolar, Founder, President & CEO, Alzheon, USA: ALZ-801: EFFICIENT ALZHEIMER'S DISEASE MODIFICATION BY PREVENTING FORMATION OF TOXIC AMYLOID AGGREGATES

Lon S. Schneider, Keck School of Medicine of the University of Southern California, USA??: A PLETHORA OF BEST TARGETS OR WINNERS' CURSES? UNTURNED STONES AND WHY TRIALS FAIL

Bengt Winblad, Karolinska Institute, Sweden: WHAT IS THE DRIVING FORCE BEHIND CLINICAL TRIALS JUMPING OVER PHASE II;INCREASED RISK FOR FAILED PHASE III?

http://adpd2017.kenes.com/scientific-information/forum-discussions#.WLWSnvkrLIU
Thanks to Rubyred77 for this link.


30-Mar-2017 17:15 19:15
S23 SYMPOSIUM
SYMPOSIUM 23 - SYNAPTIC AND CHOLINERGIC DEFICITS, Ca2+ . ER STRESS, SIGMA-1 RECEPTORS, GPCRS

Abstract:
TARGETING M1 MUSCARINIC AND SIGMA-1 RECEPTORS IN ALZHEIMER'S DISEASE: REVERSAL OF PATHOLOGICAL HALLMARKS AND ASSOCIATED COGNITIVE DYSFUNCTION IN MCGILL-R-THY1-APP RATS
Aims
Small molecules designed to target multiple receptors constitute an innovative pharmacological approach to treat disorders such as Alzheimer’s disease (AD). AF710B is a novel concomitant M1 allosteric muscarinic and sigma-1 receptor agonist, which at unmatched low doses attenuated cognitive deficits and decreased major AD-like hallmarks in 3xTg-AD mice [1]. We now report on the disease-modifying properties of AF710B in McGill-R-Thy1-APP transgenic (tg) rats.

http://cmoffice.kenes.com/ADPD17/CM.NET.WebUI/CM.NET.WEBUI.scpr/SCPRfunctiondetail.aspx?confID=05000000-0000-0000-0000-000000000195&sesID=05000000-0000-0000-0000-000000041983&absID=07000000-0000-0000-0000-000000555522


31-Mar-2017 08:00 18:00
Abstract: 109
15-MONTHS SAFETY AND EXPLORATORY EFFICACY DATA OF ANAVEX 2-73 IN A PHASE 2A STUDY IN MILD-TO-MODERATE ALZHEIMER’S DISEASE PATIENTS--author request

Abstract: 109
15-MONTHS SAFETY AND EXPLORATORY EFFICACY DATA OF ANAVEX 2-73 IN A PHASE 2A STUDY IN MILD-TO-MODERATE ALZHEIMER’S DISEASE PATIENTS--author request
Abstract not available

Co-authors
C. Missling 1
1, USA

http://cmoffice.kenes.com/ADPD17/CM.NET.WebUI/CM.NET.WEBUI.scpr/SCPRfunctiondetail.aspx?confID=05000000-0000-0000-0000-000000000195&sesID=05000000-0000-0000-0000-000000045714&absID=07000000-0000-0000-0000-000000555610
Thanks to McGuayar for this link.


01-Apr-2017 08:00 18:00
Abstract: 007
THE DUAL REGULATION OF OXIDATIVE STRESS BY SIGMA1 RECEPTORS IN PHYSIOLOGICAL OR PATHOLOGICAL CONDITIONS

Abstract: 007
THE DUAL REGULATION OF OXIDATIVE STRESS BY SIGMA1 RECEPTORS IN PHYSIOLOGICAL OR PATHOLOGICAL CONDITIONS
Aims
Mitochondrial alterations precede the appearance of pathological hallmarks in Alzheimer’s disease (AD) such as accumulation of Aß peptide and hyperphosphorylated tau protein. The sigma1 receptor (s1R) is a chaperone protein residing at mitochondria associated endoplasmic reticulum membranes and its activation by ligands stimulates neuromodulation and neuroprotection, as shown in AD models in vitro and in vivo. The s1R stabilizes Ca2+ crosstalk between ER and mitochondria and regulate hippocampal dendritic spine formation via a free radical-sensitive mechanism involving Rac1-GTP. The s1R effects on mitochondria in physiological and pathological conditions (amyloid toxicity) and its downstream signaling are not fully understood.

Method
We here evaluated the impacts of s1R ligands on reactive oxygen species (ROS) production and mitochondrial respiration and complex activities using application of amyloid-ß peptides (Aß1-42).

Results
The s1R agonists PRE084, DHEAS, ANAVEX1-41 or ANAVEX3-71 increased total ROS production in physiological condition but decreased it in pathological conditions. The s1R antagonists NE100 and progesterone had no effect. Both s1R agonists and antagonist showed no direct effect on respiration but agonists ameliorated the RCR deficit triggered by Aß1-42. We also observed that the s1R agonists increased complex I activity in physiological conditions. This effect was blocked by chelating Ca2+ with EGTA. s1R Agonists failed to affect complex II or IV activity.

Conclusion
These experiments showed that s1R activity results in a dual regulation of the mitochondrial oxidative status: in basal conditions, s1R activity triggers a moderate ROS increase, putatively used as a physiological signal, while in pathological conditions, agonists promoted a marked anti-oxidant effect.


Co-authors
T. Maurice 1, N. Goguadze 1,2, N. Natsvlishvili 2, E. Zhuravliova 2, D. Morin 3, D. Mikeladze 2
1Université de Montpellier, INSERM U 1198, Montpellier, France
2Ilia State University, Institute of Chemical Biology, Tbilisi, Georgia
3Université Paris-Est- Faculty of Medicine, UMR S955- UPEC, Creteil, France

http://cmoffice.kenes.com/ADPD17/CM.NET.WebUI/CM.NET.WEBUI.scpr/SCPRfunctiondetail.aspx?confID=05000000-0000-0000-0000-000000000195&sesID=05000000-0000-0000-0000-000000037818&absID=07000000-0000-0000-0000-000000556569
Thanks to Rubyred77 for this link.