Anavex Life Sciences Corp (AVXL)

[sokol]

The new chromatin MOA of the drug further indicates that we should be on to something extraordinarily great to the point that it boggles the mind. As Dado’s recent post says: “When you have the courage of your own convictions - you gain confidence in knowing what the future holds...”. We have been mocked and punched, but we have made so much progress over the last 5 or 6 years. Based on the chromatin MOA, we have another foundation or footing of support for our drug and its potential to treat multiple diseases. Therefore, I am more confident than ever.

Anavex 2-73 activates the Sigma-1 Receptor, which restores chromatin structures. Aberrations in chromatin remodeling proteins are found to be associated with many human diseases. This appears to have enormous implications for Anavex.

This is from the February 11 report from Anavex

"Anavex Life Sciences’ 2021 Business and Clinical Outlook:

Underlying cause of Alzheimer's disease and therapeutic intervention:

-Researchers at the University of California San Diego have identified the underlying cause of Alzheimer's disease in neurons. They discovered that changes in the structure of chromatin are responsible.2 Sigma-1 Receptor (SIGMAR1), the direct target which gets activated with ANAVEX®2-73 demonstrated to restore chromatin structures.3

-ANAVEX®2-73 linked to the prevention and treatment of age-associated diseases through induction of the autophagy “cellular recycling” process and enhanced protein clearance in cells.4"

https://www.globenewswire.com/news-release/2021/02/11/2173958/0/en/Anavex-Life-Sciences-Reports-Fiscal-2021-First-Quarter-Financial-Results-And-Business-Outlook.html

The following is from Wikipedia:

"Besides actively regulating gene expression, dynamic remodeling of chromatin imparts an epigenetic regulatory role in several key biological processes, egg cells DNA replication and repair; apoptosis; chromosome segregation as well as development and pluripotency. Aberrations in chromatin remodeling proteins are found to be associated with human diseases, including cancer. Targeting chromatin remodeling pathways is currently evolving as a major therapeutic strategy in the treatment of several cancers."

Here are two additional scientific articles supportive to the path that Anavex is pursing that may lead to treatment of multiple diseases.

1. Chromatin deregulation in disease

Abstract

"The regulation of chromatin by epigenetic mechanisms plays a central role in gene expression and is essential for development and maintenance of cell identity and function. Aberrant chromatin regulation is observed in many diseases where it leads to defects in epigenetic gene regulation resulting in pathological gene expression programmes. These defects are caused by inherited or acquired mutations in genes encoding enzymes that deposit or remove DNA and histone modifications and that shape chromatin architecture. Chromatin deregulation often results in neurodevelopmental disorders and intellectual disabilities, frequently linked to physical and developmental abnormalities, but can also cause neurodegenerative diseases, immunodeficiency, or muscle wasting syndromes. Epigenetic diseases can either be of monogenic origin or manifest themselves as complex multifactorial diseases such as in congenital heart disease, autism spectrum disorders, or cancer in which mutations in chromatin regulators are contributing factors. The environment directly influences the epigenome and can induce changes that cause or predispose to diseases through risk factors such as stress, malnutrition or exposure to harmful chemicals. The plasticity of chromatin regulation makes targeting the enzymatic machinery an attractive strategy for therapeutic intervention and an increasing number of small molecule inhibitors against a variety of epigenetic regulators are in clinical use or under development. In this review, we will give an overview of the molecular lesions that underlie epigenetic diseases, and we will discuss the impact of the environment and prospects for epigenetic therapies."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761009/

2. The Sigma-1 Receptor as a Pluripotent Modulator in Living Systems

"The sigma-1 receptor (Sig-1R) is an endoplasmic reticulum (ER) protein that resides specifically in the mitochondria-associated endoplasmic reticulum (ER) membrane (MAM), an interface between ER and mitochondria. In addition to being able to translocate to the plasma membrane (PM) to interact with ion channels and other receptors, Sig-1R also occurs at the nuclear envelope, where it recruits chromatin-remodeling factors to affect the transcription of genes. Sig-1Rs have also been reported to interact with other membranous or soluble proteins at other loci, including the cytosol, and to be involved in several central nervous system (CNS) diseases. Here, we propose that Sig-1R is a pluripotent modulator with resultant multiple functional manifestations in living systems."

https://www.sciencedirect.com/science/article/abs/pii/S0166223619302243