Three Quotations From Wikipedia On Rett Syndrome And Their Implications For ANAVEX 2-73. $AVXL

I would like to present 3 quotations fro the page on Rhett Syndrome. Let’s first tackle the big picture. https://en.wikipedia.org/wiki/Rett_syndrome

It has been argued that Rett syndrome is in fact a neurodevelopmental condition as opposed to a neurodegenerative condition. One piece of evidence for this is that mice with induced Rett Syndrome show no neuronal death, and some studies have suggested that their phenotypes can be partially rescued by adding functional MECP2 gene back when they are adults. This information has also helped lead to further studies aiming to treat the disorder.[21]

The distinction here is of primary importance. Alzheimer’s or Parkinson’s are connected to death of neurons which in their final run is undeniable. Nevertheless, the development of brain is connected in some respects with program death of neurons, apoptosis, or called pruning and growth of connections, dendrites. The observation of partial rescue in case of introducing the wild form of MECP2 gene (unmutated) is congruent with this model of development of brain as you cannot retrace the brain development and its structural changes in the brain but you can rescue the function of individual neurons. What one can gather from this is that Rett is ideally suited to be treated with gene therapy at the onset from 6 months on, or even earlier if the mutation can be detected by a test. The most striking implication for ANAVEX 2-73 Blarcamesine that it works by altering the brain wide concentration of basics neurotransmitters like Glutamate and GABA. Both of these are involved in about 90% of all synaptic connections in brain. Excessive amounts of Glutamate are connected to Lou Gehrig disease (ALS), Alzheimer’s and seizures, among others. I think that both Glutamate and GABA are two neurotransmitters concentration to the easiest to measure currently without autopsy. This is the 30,000 feet view of the disease. Yet, it is very valuable since it measures the global disruption to normal function of most of the synaptic connection and its improvement alike measures homeostatic equilibrium moving in the desired direction. Nevertheless, researchers try to pin point the exact epicenter of the disruption cause by the genetic mutation in MECP2.

Researchers have concluded that “Because these neurons are a pivotal source of norepinephrine throughout the brainstem and forebrain and are involved in the regulation of diverse functions disrupted in Rett syndrome, such as respiration and cognition, we hypothesize that the locus coeruleus is a critical site at which loss of MECP2 results in CNS dysfunction.” The restoration of normal locus coeruleus function may therefore be of potential therapeutic value in the treatment of Rett syndrome.[29][30]

I do not have much to comment as I can only touch on matter of concepts and this goes into deatails which make a web of links between multitude of findings, papers and molecules. I will repeat that SIGMAR1R is connected in broad sense with homeostasis, and in more deatil to synthesis and “quality control” of proteins, synaptic potential and oxidative stress. Blarcamesine can not replace the completeness of gene therapy, but can alter the broad chemistry of the patients brains. This is indeed an amazing feat for an CNS drug in genetic disease. I am tempted to venture here into the unknow sea to me. I have checked what locus coeruleus is. It is located in lower brain and tied to reaction to stress and panic itself. If it can somehow deregulate Glutamate and GABA, it would be driving brain to “overexitation”, as if in biochemical equivalent of state of panic, stress, overpowering the inhibiting mechanism on synaptic level. That might not be true (!), but to my layperson mind it makes a good description of the gist of that quatation. Is the Blarcamesine working on Glutamate or GABA “level” directly or if I can venture, on the level of locus coeruleus, or somewhere in betweeen? A 64 billion dollar question?

RTT pathology, in some aspects, overlaps the motor phenotype observed in PD patients.[39][40][41] Several neuropathological studies on postmortem brain samples argued for an SNpc alteration evidenced by neuromelanin hypopigmentation, reduction in the structure area, and even controversial, signs of apoptosis. In parallel, an hypometabolism was underlined by a reduction of several catecholamines (dopamine, noradrenaline, adrenaline) and their principal metabolic by-products.[26] Mouse models of RTT are available and the most studied are constitutively deleted Mecp2 mice developed by Adrian Bird or Rudolf Jaenisch laboratories.[42][43][44][45]

The only part I can digest here, is that the autopsies point to similar effects on neurons on cellular in Rett and Parkinson’s. In light of recent release of trial for ANAVEX 2-73 in Parkinson’s Phase2 the quatotation increases hopes for substential theurapetic effect in Rett patients.

In the above discussion I concentrated on the neurotrasmmitters and not the measures of patients progress in behavior. For care givers and parents these are a Godsent, but on my level would require thourogh understading of the symptoms. That is a domain of pratictioners in medicine and not blogers who never interacted with a stricken child or parents so I limit my entry to neutrasmitters.

George, I think you wanted me to write somthing about Rett, so here it is.

Also, thanks to Joseph f. for a donation, it is duly appreciated. All the best to you! Thank you.

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2 thoughts on “Three Quotations From Wikipedia On Rett Syndrome And Their Implications For ANAVEX 2-73. $AVXL

  1. If 2-73 works for Rett syndrome I believe it will work for Autism…

    “Opinion
    The Neurochemistry of Autism
    Rosa Marotta 1 , Maria C. Risoleo 1,2, Giovanni Messina 3 , Lucia Parisi 4,y,
    Marco Carotenuto 2,y , Luigi Vetri 5,* and Michele Roccella 4,y

    Received: 20 February 2020; Accepted: 10 March 2020; Published: 13 March 2020

    Abstract: Autism spectrum disorder (ASD) refers to complex neurobehavioral and neurodevelopmental conditions characterized by impaired social interaction and communication, restricted and repetitive patterns of behavior or interests, and altered sensory processing. Environmental, immunological, genetic, and epigenetic factors are implicated in the pathophysiology of autism and provoke the occurrence of neuroanatomical and neurochemical events relatively early in the development of the central nervous system. Many neurochemical pathways are involved in determining ASD; however, how these complex networks interact and cause the onset of the core symptoms of autism remains unclear. Further studies on neurochemical alterations in autism are necessary to clarify the early neurodevelopmental variations behind the enormous heterogeneity of autism spectrum disorder, and therefore lead to new approaches for the treatment and prevention of autism. In this review, we aim to delineate the state-of-the-art main research findings about the neurochemical alterations in autism etiology, and focuses on gamma aminobutyric acid (GABA) and glutamate, serotonin, dopamine, N-acetyl aspartate, oxytocin and arginine-vasopressin, melatonin, vitamin D, orexin, endogenous opioids, and acetylcholine. We also aim to suggest a possible related therapeutic approach that could improve the quality of ASD interventions. Over one hundredreferences were collected through electronic database searching in Medline and EMBASE (Ovid),Scopus (Elsevier), ERIC (Proquest), PubMed, and the Web of Science (ISI).Keywords: autism spectrum disorder; neurochemistry; GABA; glutamate; serotonin;”

    https://www.mdpi.com/2076-3425/10/3/163/pdf

    1. I am reading this paper. It is an overview of many other more detail studies on autism. The amount of information overwhelms my memory. It usually takes years of study to comprehend all the connections involved. What my limited understanding tells is that this paper suggests that the disturbance in homeostasis of neurotransmitters might both a cause and/or a symptom of Autism. If we are to look for primary cause, as I suspect a cascades are usually involved, these may start with genetic, to structural, that is dis function, however caused in one part of brain can affect homeostasis of the whole through imbalance in neurotransmitters. I need to start working on new post. Thank you, Xena for this paper.

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