Fascinating post, MD Virologist. Perhaps you will entertain a few questions on which I would say you are uniquely qualified to offer a perspective.
It appears to me that CCR5/CCL5/RANTES has emerged suddenly and unexpectedly as a critical pathway in many diseases.
Am I imagining that sudden emergence? As physician and/or scientist in this field, do you find the emergence of CCR5/CCL5/RANTES to be a relatively new, and somewhat sudden, research area?
The emergence of leronlimabCYDY for covid19 is so interesting for so many personal, scientific, economic, and business issues.
It almost seems as if Patterson's potentially watershed RANTES/covid19 publication is a key that will unlock development efforts in many different, and previously unrelated, diseases. All because of the previously unknown, or at least untargeted, CCR5/CCL5 immune function.
It is quite remarkable how the CCR5/CCL5 axis appears so powerful in so many disease conditions, and it seems equally remarkable that the CCR5/CCL5 axis has not been previously targeted in any of these diseases.
Blood CCL5 chemokine gradient propels immune cells to the locations of tumors and inflammation. In solid tumors, the CCR5/CCL5 axis and CCL5 chemokine gradient may play a key role in how the tumor microenvironment prevents infiltration of cancer killing immune cells. In covid19, the CCL5 chemokine gradient may be the primary factor that causes cytokine syndrome.
In other autoimmune diseases besides covid19 such as MS or alzheimers, the CCL5 chemokine gradient may be the cause of excessive immune cell infiltration and damage.
In metastatic solid tumors where the tumor cells overexpress CCR5, the CCR5 receptor activation seems to confer some sort of motility upon the cancer cell which causes the the cancer cell to leave the tumor, enter the bloodstream, and travel to some other tissue to cause a metastatic tumor.
No doubt the mechanism of action for some lernlimab results is still unknown. In Patterson's preprint, repolarization of macrophages is an important result. Patterson's covid19 macrophage result is entirely concordant with the covid19 results of lenzilumab and mavrilinumb, which are antibodies to granulocyte macrophage colony stimulating factor (GMCSF). Why is it that antibodies binding GMCSF in blood has the same effect as blocking activation of CCR5 on the macrophages?
For some CCR5 blocker immune applications, the reason for CCR5 involvement in inflammation may as yet be completely undiscovered. This might be the case for the leronlimab mouse studies in MS, which the researchers described as "never having seen results like that before".
For all of these diseases, it seems the state-of-the-art has suddenly stumbled upon the importance of CCR5/CCL5 in all of these diseases, and Cytodyn is the tip of the spear.
What I wonder is: Given the multiplicity of diseases that might be targeted with a CCR5 blocking molecule, how come there are no candidate molecules for the task? Seems to me its leronlimab and maraviroc. And both of those were developed for HIV.
clinicaltrials.gov reports 75,488 results for the search term "cancer".
Add CCL5, and there are 11 results. Add RANTES, and there are 9 results. Add CCR5, and there are 19 results.
So of 75,488 clinical cancer trials only 39 even measure CCR5/CCL5/RANTES, let alone posit them as primary factors. That's less than one out of one thousand human clinical trials.
MD Virologist, can you comment on what appears to me to be this situation where RANTES/CCL5/CCL4 has been totally overlooked as to its potential primary involvement in many diseases?
If it has been overlooked, what might be the reason for that?
And I wonder about the extent to which Patterson expected to find RANTES as the cause of covid19?
Do you think he anticipated that CCR5 receptor mediated chemotaxis might be the cause of covid19 cytokine response syndrome? Or was he just taking some wild guesses?
The emergence of leronlimab/CYDY for covid just seems so much like a bolt of lightning from a clear blue sky.
Why didn't anyone think of this before?
My favorite comment from Pourhassan is from the April 27 youtube:
...we were not on the map (for Covid19). Nobody thought we were on the map (for Covid19) and we didn't know either. Dr. Patterson and Dr. Scott Kelly had talked about it and then when Dr. Harish Seethamraju from Montefiore Medical Center heroically came and said "I need this" that started everything.
It seems like nobody had a clue that the CCL5 chemokine gradient was attracting the excessive immune response. And then suddenly the CCL5 chemokine gradient makes sense in so many other diseases.
It appears to me that CCR5/CCL5/RANTES has emerged suddenly and unexpectedly as a critical pathway in many diseases.
Am I imagining that sudden emergence? As physician and/or scientist in this field, do you find the emergence of CCR5/CCL5/RANTES to be a relatively new, and somewhat sudden, research area?
The emergence of leronlimabCYDY for covid19 is so interesting for so many personal, scientific, economic, and business issues.
It almost seems as if Patterson's potentially watershed RANTES/covid19 publication is a key that will unlock development efforts in many different, and previously unrelated, diseases. All because of the previously unknown, or at least untargeted, CCR5/CCL5 immune function.
It is quite remarkable how the CCR5/CCL5 axis appears so powerful in so many disease conditions, and it seems equally remarkable that the CCR5/CCL5 axis has not been previously targeted in any of these diseases.
Blood CCL5 chemokine gradient propels immune cells to the locations of tumors and inflammation. In solid tumors, the CCR5/CCL5 axis and CCL5 chemokine gradient may play a key role in how the tumor microenvironment prevents infiltration of cancer killing immune cells. In covid19, the CCL5 chemokine gradient may be the primary factor that causes cytokine syndrome.
In other autoimmune diseases besides covid19 such as MS or alzheimers, the CCL5 chemokine gradient may be the cause of excessive immune cell infiltration and damage.
In metastatic solid tumors where the tumor cells overexpress CCR5, the CCR5 receptor activation seems to confer some sort of motility upon the cancer cell which causes the the cancer cell to leave the tumor, enter the bloodstream, and travel to some other tissue to cause a metastatic tumor.
No doubt the mechanism of action for some lernlimab results is still unknown. In Patterson's preprint, repolarization of macrophages is an important result. Patterson's covid19 macrophage result is entirely concordant with the covid19 results of lenzilumab and mavrilinumb, which are antibodies to granulocyte macrophage colony stimulating factor (GMCSF). Why is it that antibodies binding GMCSF in blood has the same effect as blocking activation of CCR5 on the macrophages?
For some CCR5 blocker immune applications, the reason for CCR5 involvement in inflammation may as yet be completely undiscovered. This might be the case for the leronlimab mouse studies in MS, which the researchers described as "never having seen results like that before".
For all of these diseases, it seems the state-of-the-art has suddenly stumbled upon the importance of CCR5/CCL5 in all of these diseases, and Cytodyn is the tip of the spear.
What I wonder is: Given the multiplicity of diseases that might be targeted with a CCR5 blocking molecule, how come there are no candidate molecules for the task? Seems to me its leronlimab and maraviroc. And both of those were developed for HIV.
clinicaltrials.gov reports 75,488 results for the search term "cancer".
Add CCL5, and there are 11 results. Add RANTES, and there are 9 results. Add CCR5, and there are 19 results.
So of 75,488 clinical cancer trials only 39 even measure CCR5/CCL5/RANTES, let alone posit them as primary factors. That's less than one out of one thousand human clinical trials.
MD Virologist, can you comment on what appears to me to be this situation where RANTES/CCL5/CCL4 has been totally overlooked as to its potential primary involvement in many diseases?
If it has been overlooked, what might be the reason for that?
And I wonder about the extent to which Patterson expected to find RANTES as the cause of covid19?
Do you think he anticipated that CCR5 receptor mediated chemotaxis might be the cause of covid19 cytokine response syndrome? Or was he just taking some wild guesses?
The emergence of leronlimab/CYDY for covid just seems so much like a bolt of lightning from a clear blue sky.
Why didn't anyone think of this before?
My favorite comment from Pourhassan is from the April 27 youtube:
...we were not on the map (for Covid19). Nobody thought we were on the map (for Covid19) and we didn't know either. Dr. Patterson and Dr. Scott Kelly had talked about it and then when Dr. Harish Seethamraju from Montefiore Medical Center heroically came and said "I need this" that started everything.
It seems like nobody had a clue that the CCL5 chemokine gradient was attracting the excessive immune response. And then suddenly the CCL5 chemokine gradient makes sense in so many other diseases.
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