Anavex Life Sciences Corp (AVXL)

[sokol]

How may AVXL 2-73 benefit patients with Parkinson's dementia? Perphaps some understanding of autophagy or the cellular recycling process helps to answer this question. See the six references below.

1. Regulation and Function of Autophagy during Cell Survival and Cell Death

https://cshperspectives.cshlp.org/content/4/6/a008813.full

''Autophagy is an important catabolic process that delivers cytoplasmic material to the lysosome for degradation. Autophagy promotes cell survival by elimination of damaged organelles and proteins aggregates, as well as by facilitating bioenergetic homeostasis. Although autophagy has been considered a cell survival mechanism, recent studies have shown that autophagy can promote cell death. The core mechanisms that control autophagy are conserved between yeast and humans, but animals also possess genes that regulate autophagy that are not present in yeast. These regulatory differences may be explained by the need to control autophagy in a cell context-specific manner in multicellular animals, such as during cell survival and cell death. Autophagy was thought to be a bulk cytoplasmic degradation mechanism, but recent studies have shown that specific cargo is recruited for degradation. This suggests the possibility that either cell survival or death may be regulated by selective autophagic clearance of cytoplasmic material. Here we summarize the mechanisms that regulate autophagy and how they may contribute to cell survival and death.

....Autophagy is involved in maintaining cellular homeostasis......

The complex roles of autophagy in survival and death should also be considered when designing therapies for other disorders. Autophagy promotes the clearance of protein aggregates (Hara et al. 2006; Komatsu et al. 2006) and has an important neuroprotective role in several neurodegenerative disease models, including Alzheimer's and Huntington's (Menzies et al. 2011). In addition, recent evidence suggests that mitochondrial autophagy plays an important role in the pathogenesis of Parkinson's disease (Nixon and Yang 2012). Although the promotion of autophagy in neurodegenerative disease models results in healthier individuals, it is also possible that too much autophagy could have deleterious effects, including problems with bioenergetics or even worse killing the cells while trying to protect them. Future work should not only consider how autophagy may promote cell survival or death, but what the impact of modulating autophagy may have on the health of the test subject and patient......''

2. Anavex Life Sciences Reports Publication of New Data that Show ANAVEX®2-73 Induces Cellular Recycling Process Linked to the Prevention and Treatment of Age-Associated Diseases

https://www.globenewswire.com/news-release/2019/03/04/1745838/0/en/Anavex-Life-Sciences-Reports-Publication-of-New-Data-that-Show-ANAVEX-2-73-Induces-Cellular-Recycling-Process-Linked-to-the-Prevention-and-Treatment-of-Age-Associated-Diseases.html

'..... activation of Sig-1R with ANAVEX®2-73 leads to the prominent induction of the autophagy “cellular recycling” process and enhanced protein clearance in cells. The study, led by Christian Behl et. al. of the University Medical Center at Johannes Gutenberg University, in Mainz, Germany, has been published in the peer-reviewed journal, Cells (link).

There is a great amount of data linking dysfunction and malfunction of autophagy to neurodegenerative disease and, consistent with its role in proteostasis, to the accumulation of protein aggregates. Thus, the modulation of autophagy has become one key pharmacological target in neurodegeneration,” the researchers reported. “In fact, there are multiple overlaps of autophagy and pathogenesis pathways in Alzheimer’s disease, Parkinson’s disease, and ALS. Recently different alternative views and new pharmacological targets towards Alzheimer’s prevention and treatment are evolving and include a strong focus on the autophagy process.”

The Cells paper also noted that this is the ?rst report to show that Sig-1R activation enhances the autophagic ?ux in human cells and in C. elegans with positive effects on proteostasis in vitro and in vivo, an important concept towards the stabilization of neuronal survival and function that may help to prevent age-associated neurodegeneration.

The paper entitled, “Sigma-1 Receptor Activation Induces Autophagy and Increases Proteostasis Capacity In Vitro and In Vivo,” can be found online on the Cells website.'

3. Role of Autophagy in Parkinson's Disease.

https://www.ncbi.nlm.nih.gov/pubmed/29484979

"Autophagy is an essential catabolic mechanism that delivers misfolded proteins and damaged organelles to the lysosome for degradation. Autophagy pathways include macroautophagy, chaperone-mediated autophagy and microautophagy, each involving different mechanisms of substrate delivery to lysosome. Defects of these pathways and the resulting accumulation of protein aggregates represent a common pathobiological feature of neurodegenerative disorders such as Alzheimer, Parkinson and Huntington disease.

....pharmacological targets and therapeutic strategies that, by boosting autophagy, may be theoretically beneficial for PD.''

4. About Parkinson's disease dementia

https://www.arthritisusa.net/Neuro-Degenerative-Diseases


''The brain changes caused by Parkinson's disease begin in a region that plays a key role in movement. As Parkinson's brain changes gradually spread, they often begin to affect mental functions, including memory and the ability to pay attention, make sound judgments and plan the steps needed to complete a task.

The key brain changes linked to Parkinson's disease and Parkinson's disease dementia are abnormal microscopic deposits composed chiefly of alpha-synuclein, a protein that's found widely in the brain but whose normal function isn't yet known. The deposits are called "Lewy bodies".

Lewy bodies are also found in several other brain disorders, including dementia with Lewy bodies (DLB). Evidence suggests that dementia with Lewy bodies, Parkinson's disease and Parkinson's disease dementia may be linked to the same underlying abnormalities in brain processing of alpha-synuclein.

Another complicating factor is that many people with both dementia with Lewy bodies and Parkinson's disease dementia also have plaques and tangles — hallmark brain changes linked to Alzheimer's disease.''

5. Phase 2 Study of Potential Oral Therapy for Parkinson’s Dementia, Anavex 2-73, Planned

https://parkinsonsnewstoday.com/2018/04/20/anavex-planning-phase-2-trial-of-potential-parkinsons-dementia-oral-therapy/

'According to the Parkinson’s Foundation, around 50 to 80 percent of Parkinson’s patients will develop disease-related dementia. Parkinson’s is characterized by the loss of neurons in a crucial brain area that controls movement, the substantia nigra. This loss, in turn, lowers brain levels of dopamine, a key player in nerve cell or neuronal communication.

With disease progression, these changes spread to other areas of a patient’s brain, affecting memory, attention, and thinking and reasoning.

“As many as 80 percent of people with Parkinson’s will experience Parkinson’s disease dementia and treatment options are limited,” Christopher Missling, president and CEO at Anavex, said in a press release.

Results of preclinical work, fully funded by the The Michael J. Fox Foundation for Parkinson’s Research, show that treatment with Anavex 2-73 was able to restore function to damaged nerve cells in mouse models of Parkinson’s disease. Data also demonstrated that it targets misfolded proteins and poorly working mitochondria — a cell’s energy source — to prevent oxidative stress, inflammation, and cellular stress.'

6. New way to stimulate cellular recycling process

https://www.sciencedaily.com/releases/2018/05/180515162807.htm

"Brown University researchers studying the biology of aging have demonstrated a new strategy for stimulating autophagy, the process by which cells rebuild themselves by recycling their own worn-out parts."

Comment: AVXL 2-73 may be a drug that treats aging in general as well as various diseases that are associated with aging. The FDA does not recognize aging as a disease, but if this drug ever gains approval for any use, it will be demanded by aging patients (baby boomers) and prescribed off label by physcians.