Anavex Life Sciences Corp (AVXL)

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Anavex 2-73 Prevention of Onset of Alzheimer’s Disease

ROS may be an underlying cause of neurodegeneration. Anavex 2-73 blocks oxidative stress and may prevent the onset of Alzheimer's. There is a strong association between the detection of increased ROS production and the increased oxidative damage observed in CNS disorders such as Parkinson's disease, Alzheimer's disease and ALS. Oxidative stress can also impair mitochondrial function, leading to a deple­tion of ATP and decreased antioxidant capacity. One of the most accepted hypotheses for AD onset implicates that mitochondrial dysfunction and oxidative stress are one of the primary events in the insurgence of the pathology.


1. Oxidative and nitrosative stress

Oxygen (O2) is critical to meet the energetic demands of bio­logical tissues through the production of ATP by oxidative phos­phorylation. However, aberrant O2 reduction produces radical species that can cause extensive damage to cellular components, cells, and tissues. This phenomenon of “oxidative stress” is de?ned by a broad range of phenotypes, including the accumulation of oxidized molecules and the disruption of normal cellular processes and viability. Oxidative stress is typically considered to be the state inwhich these phenotypes are measurable at higher levels than in a “normal” state. Neurons may be particularly vulnerable to oxidative stress due to their terminally differentiated state, complex morphology, and dependence on surrounding glia for metabolic substrates and glutathione (12). Reactive oxygen species (ROS) are generated by multiple conditions and sources, including sustained neurotransmission (e.g., of glutamate, dopamine, or serotonin), mitochondrial dysfunction, and production by glial cells. Depend­ing on the species and location of the ROS, oxidative damage can affect nucleic acids, proteins and lipids. The best evidence that ROS may be an underlying cause of neurodegeneration is the strong association between the detection of increased ROS production and the increased oxidative damage observed in CNS disorders such as Parkinson's disease, Alzheimer's disease and ALS (12,13). Oxidative stress can also impair mitochondrial function, leading to a deple­tion of ATP and decreased antioxidant capacity (13). Along with ROS, reactive nitrogen species (RNS) can also be generated under pathological conditions in the CNS.

https://www.researchgate.net/profile/Linda-Nguyen-8/publication/271530073_Role_of_sigma-1_receptors_in_neurodegenerative_diseases/links/54cbf4500cf29ca810f4858f/Role-of-sigma-1-receptors-in-neurodegenerative-diseases.pdf?origin=publication_detail


2. ANAVEX 2-73 shown to block oxidative stress, preventing onset of Alzheimer's disease
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Anavex Life Sciences Corp.
Oct 18, 2012, 09:00 ET
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Data presented at Neuroscience 2012

VANCOUVER, Oct. 18, 2012 /PRNewswire/ - Anavex Life Sciences Corp. ("Anavex") (OTCQB: AVXL) today unveiled more promising new data regarding ANAVEX 2-73, the company's drug candidate for the treatment and modification of Alzheimer's disease currently in human clinical trials. The confidential status of the new ANAVEX 2-73 data has been lifted now that a formal presentation has been made at Neuroscience 2012 in New Orleans.

ANAVEX 2-73 demonstrated its ability to restore mitochondrial functionality, and prevent oxidative stress and apoptosis (cell death) in a scientific study at the University of Montpellier and INSERM, in France. Mitochondrial dysfunction caused by amyloid peptide toxicity has been consistently reported as an early event in Alzheimer's physiopathology and a telltale sign of the disease, appearing before amyloid-beta plaque deposits and memory deficits in patients.

"This new study emphasizes the effective mitochondrial neuroprotection provided by ANAVEX 2-73," said Tangui Maurice, PhD, CNRS Research Director, Head of Team 2 'Endogenous Neuroprotection in Neurodegenerative Diseases', at the University of Montpellier and INSERM. "The Anavex compound effectively restored mitochondrial respiration and integrity. This restorative effect decreases oxidative stress and disrupts Alzheimer's disease well before plaques can start to accumulate and memory loss begins."

A selective sigma-1 agonist reference drug showed similar results in the study, confirming the sigma-1 chaperone protein activation by ANAVEX 2-73.

This new data was presented at Neuroscience 2012, the premier venue for neuroscientists from around the world to debut cutting-edge research on the brain and nervous system, held this week in New Orleans. The presentation is titled, "Mitochondrial protection is induced by the novel tetrahydrofuran derivative ANAVEX 2-73 after ICV injection of oligomeric Aß25-35 peptide in mice, a nontransgenic Alzheimer's disease model."

The study was jointly conducted by Valentine Lahmy, PharmD, Romain Long, PhD, Didier Morin, PhD, team leader at INSERM, Institut Henri Modor, Créteil, Vanessa Villard, PhD, CEO of Amylgen, Alexandre Vamvakides, PhD, Chief Scientific Officer and Scientific Founder of Anavex, and Tangui Maurice, PhD. Full details of the study are described on Anavex's website at http://www.anavex.com/files/2012-10-17_ANAVEX_2-73_poster_Neuroscience_2012.pdf.

https://www.prnewswire.com/news-releases/anavex-2-73-shown-to-block-oxidative-stress-preventing-onset-of-alzheimers-disease-174759041.html

3. Mitochondrial Dysfunction: Different Routes to Alzheimer’s Disease Therapy

https://downloads.hindawi.com/journals/omcl/2014/780179.pdf