Anavex Life Sciences Corp (AVXL)

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Commentary for: Functional Significance of Endothelial Sigma-1 Receptors in Vascular Reactivity and Barrier Function

Article: https://digitalcommons.usf.edu/etd/8972/?fbclid=IwAR0V6gtYi_5Bv_we8vuUg7H_6BwHwzsoQkkxS0qLQ3lbCXby4gpRHhxJr4Y

Pretty neat read about S1R activation and its effect on endothelial cells. Endothelial cells form a thin barrier which line all blood vessels and regulate metabolic exchanges (nitric oxide, sugar, water, waste, etc.) from within the bloodstream and the individual cells – much like how the blood brain barrier protects the brain from most toxins and regulates what comes in and out. Another similarity to the blood brain barrier is the endothelial cell’s ability to degrade and become ‘leaky’, which has several detriments to the cardiovascular system.

The researchers were able to find that S1R agonists maintained endothelial cell integrity, and “relaxed rat mesenteric lymphatic vessels”. Mesenteric lymphatic vessels are used for glucose metabolism. The functional status of lymphatic muscle and endothelial cells is an important factor that supports fluid and macromolecule exchange and immune cell trafficking through the body and is also crucial to the transport of lipids (fat) adsorbed in small intestine.

A peer review journal expanded upon the importance of vascular endothelium, “A growing list of conditions, including those commonly associated as risk factors for atherosclerosis such as hypertension, hypercholesterolemia, smoking, diabetes mellitus and heart failure are associated with diminished release of nitric oxide (NO) into the arterial wall either because of impaired synthesis or excessive oxidative degradation. The decreased production of NO in these pathological states cause serious problems in endothelial equilibrium and that is the reason why numerous therapies have been investigated to assess the possibility of reversing endothelial dysfunction by enhancing the release of nitric oxide from the endothelium.”

The above excerpt is important as it mentions diminished nitric oxide as a significant catalyst for hypertension, diabetes, heart failure, etc. When researchers tested S1R agonists in cultured lymphatic endothelial cells (petri dish), S1R prompted elevated levels of nitric oxide. It is unclear from the publication if S1R brought NO back to normal levels, but any addition to vascular homeostasis is surely welcomed and is supported further by Anavex’s preclinical/clinical data. I continue to be impressed by the vast array of clinical benefit derived from S1R elevation.

Some of Anavex’s publications supporting S1R as a cardiovascular solvent:
Anavex Life Sciences Announces Notice of Allowance for U.S. Patent Application ANAVEX®2-73
Anavex Life Sciences Reports Potential Normalization of Hypertension with ANAVEX®2-73
Anavex: Research Report Reveals Cardioprotective Action of Sigma-1 Receptor Agonists

(Shoutout to DG for the cool find)