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Posted On: 01/16/2021 3:34:10 PM
Post# of 148908
Next weeks will be crucial in the launch of CYDY as a global force in the treatment of various diseases. A favorable result in COVID CD-12 trial (less than 50 deaths) will mean a step increase in SP, a more robust financing allowing the company to pursue multiple indications (mostly, I hope Oncology) and the beginning of the route to three-digit valuations.
So, anxiously we wait.
In the mean time I was trying to make a mental go-back evaluating the chances we have to help the sufferers in a worsening pandemic and get approved. When I do this exercise, I tend to refer to the science and, to a less extent to the results obtained so far (clinical) that should be mere demonstration that the former has a solid foundation and it works.
Wanted to share with you my thoughts and a recent “discovery” (just for me as I know some of you have gone through this long time ago).
COVID is a damn difficult condition to treat as several attempts have failed. We know some drugs work a little bit and some that don’t work The discussion is long and sometimes politically charged, but basically it seems that the virus is advancing faster than our ability to treat it. Fortunately, high efficacy vaccines have been developed rapidly.
There are three ways COVID attacks our immune system:
1) Cytokine storms created by recruited immune cells. Abnormally high levels of IL-6, TNF-a, IL-1b, IL-12 and other otherwise unusual cytokines (IL-5 and IL-17) and chemokines such as CCL2, CCL7, CXCL9, IL-8 and RANTES who summon in cells to join the fight. The cycle of inflammation damages the lung tissue resulting in ARDS.
2) In severely ill patients’ T cells behave differently. In the case of an infection T cells that kills antigens grow on number during the infection, however his is not the case in the sickest COVID patients. This deficit of T cells lasts for long time. Some chemokines like CXCl9 and CXCL10 that direct cells to the infected sites are there, however not the respective T-cells. So far there is not a good explanation of why they are not there or why they just died. Answering why are T cells disappearing is an important landmark in fighting COVID (it might very well be that COVID itself is killing them or the bone marrow is somehow being affected by COVID)
3) NETs (Neutrophil Extracellular Traps) discovered 11 or so years ago are used in the cells by neutrophils to eliminate viruses and other pathogens. However, in COVID during the inflammation hey can turn toxic and produce blood cloths that damage the lungs and other organs. Basically an excess of NETs create clothing and blockage of blood vessels. In addition of physical obstruction NETs can degrade protein that inhibit blood coagulation producing multiple organs failure.
We know that Vyrologix (VX) can help with the two first items, that is stopping the cytokine storms and restoring T cell ratios to healthy levels (the biggest triumph imo), however, I was a bit bothered asking myself: what if we cannot help with the NET part of COVID? We will need a combo in the future that will help with the clothing as well.
In doing some research I discovered some evidence that we can help with the NET problem as well
(I am sleeping better now). What is more, we could do a trial for ALI (acute lung injury) .
From the article:
https://ashpublications.org/blood/article/123...-chemokine
This is long already but basically we have a drug that can address the three main modes of action of COVID-19 !!! Restoration of T-cell count being the most important but addressing cytokine storms and vessel/organ clothing as well. The latter a pleasant surprise for me. And a possible new indication for VX (non COVID-related ALI).
Let’s wait for the results to demonstrate that SCIENCE works. However, I am more calm now.
For those with lots of time in their hands due to the long weekend, please find below some more info on NETs
A Comparative Review of Neutrophil Extracellular Traps in Sepsis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280561/
Neutrophil Extracellular Traps and Its Implications in Inflammation: An Overview
https://www.frontiersin.org/articles/10.3389/...00081/full
You all have a great weekend !!!!
So, anxiously we wait.
In the mean time I was trying to make a mental go-back evaluating the chances we have to help the sufferers in a worsening pandemic and get approved. When I do this exercise, I tend to refer to the science and, to a less extent to the results obtained so far (clinical) that should be mere demonstration that the former has a solid foundation and it works.
Wanted to share with you my thoughts and a recent “discovery” (just for me as I know some of you have gone through this long time ago).
COVID is a damn difficult condition to treat as several attempts have failed. We know some drugs work a little bit and some that don’t work The discussion is long and sometimes politically charged, but basically it seems that the virus is advancing faster than our ability to treat it. Fortunately, high efficacy vaccines have been developed rapidly.
There are three ways COVID attacks our immune system:
1) Cytokine storms created by recruited immune cells. Abnormally high levels of IL-6, TNF-a, IL-1b, IL-12 and other otherwise unusual cytokines (IL-5 and IL-17) and chemokines such as CCL2, CCL7, CXCL9, IL-8 and RANTES who summon in cells to join the fight. The cycle of inflammation damages the lung tissue resulting in ARDS.
2) In severely ill patients’ T cells behave differently. In the case of an infection T cells that kills antigens grow on number during the infection, however his is not the case in the sickest COVID patients. This deficit of T cells lasts for long time. Some chemokines like CXCl9 and CXCL10 that direct cells to the infected sites are there, however not the respective T-cells. So far there is not a good explanation of why they are not there or why they just died. Answering why are T cells disappearing is an important landmark in fighting COVID (it might very well be that COVID itself is killing them or the bone marrow is somehow being affected by COVID)
3) NETs (Neutrophil Extracellular Traps) discovered 11 or so years ago are used in the cells by neutrophils to eliminate viruses and other pathogens. However, in COVID during the inflammation hey can turn toxic and produce blood cloths that damage the lungs and other organs. Basically an excess of NETs create clothing and blockage of blood vessels. In addition of physical obstruction NETs can degrade protein that inhibit blood coagulation producing multiple organs failure.
We know that Vyrologix (VX) can help with the two first items, that is stopping the cytokine storms and restoring T cell ratios to healthy levels (the biggest triumph imo), however, I was a bit bothered asking myself: what if we cannot help with the NET part of COVID? We will need a combo in the future that will help with the clothing as well.
In doing some research I discovered some evidence that we can help with the NET problem as well
(I am sleeping better now). What is more, we could do a trial for ALI (acute lung injury) . From the article:
https://ashpublications.org/blood/article/123...-chemokine
Quote:
Activated neutrophils can release neutrophil extracellular traps (NETs) that are composed of DNA fibers decorated with histones and granule proteins. NETs exhibit antimicrobial functions by trapping and killing extracellular pathogens in blood and tissues during infection. However, when produced at the wrong time or in the wrong amount, NETs can also have a negative effect on the host. It has been shown that NETs contribute to the pathology of several inflammatory diseases. It has been recently demonstrated that intimate platelet-neutrophil interactions induce the formation of neutrophil extracellular traps under inflammatory conditions. However, the molecular mechanisms by which neutrophil extracellular traps are formed during acute lung injury (ALI) are poorly understood.
Quote:
ALI is a life-threatening disease that can develop in the course of different clinical conditions such as acid aspiration, pneumonia, or prolonged mechanical ventilation, and contributes significantly to critical illness. Recent epidemiological studies demonstrated that the incidence of ALI is very high and, despite all innovations in intensive care medicine, the mortality of this disease remains as high as 40% . The pathogenesis of ALI is characterized by an influx of a protein-rich edema fluid into the interstitial and intra-alveolar spaces as a consequence of increased permeability of the alveolar-capillary barrier in conjunction with excessive invasion of inflammatory cells—particularly neutrophils. Despite extensive research into the pathogenesis of ALI and many clinical trials testing new medications, there is no effective therapeutic agent to treat patients with this syndrome. More research is desperately required to discover novel pathways that can be targeted with new treatment options.
Quote:
Neutrophil recruitment and an increased vascular permeability are hallmarks of ALI. Local and systemic hypoxia during ALI activates the transcriptional factor HIF-1, leading to an activation and recruitment of myeloid cells. Hypoxia during inflammation may also contribute to NET formation. Recent publications suggest that platelet-induced NETs are also involved in the pathogenesis of ALI and may influence vascular permeability. Mechanistically, we identify platelet-derived CXCL4 and CCL5 as crucial mediators in forming NETs. Previous work has demonstrated that heterodimerization of platelet-derived CCL5 and CXCL4 enhances their ability to activate and recruit inflammatory cells. By using a synthetic peptide, termed MKEY, which specifically disrupts the synergistic interaction between CXCL4 and CCL5, we were able to show that this peptide reduces the formation of platelet-neutrophil aggregates and thus abrogates NET formation, neutrophil recruitment, and vascular permeability increase , and improves gas exchange. In line with models of vascular recruitment, these data imply that the CCL5 receptors CCR1 and CCR5, which support the CCL5-CXCL4 heteromer activity, are the GPCRs responsible for mediating NET formation together with integrins
This is long already but basically we have a drug that can address the three main modes of action of COVID-19 !!! Restoration of T-cell count being the most important but addressing cytokine storms and vessel/organ clothing as well. The latter a pleasant surprise for me. And a possible new indication for VX (non COVID-related ALI).
Let’s wait for the results to demonstrate that SCIENCE works. However, I am more calm now.
For those with lots of time in their hands due to the long weekend, please find below some more info on NETs
A Comparative Review of Neutrophil Extracellular Traps in Sepsis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280561/
Neutrophil Extracellular Traps and Its Implications in Inflammation: An Overview
https://www.frontiersin.org/articles/10.3389/...00081/full
You all have a great weekend !!!!
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