Modest Correlation of the New Experts with Potential New Indications for CCR5 Inhibition
Dr. Paul Edison , more than likely brought on board for the indication of Alzheimer's Disease and possibly epilepsy. His work in assessing microglial activation and amyloid load showed that both these are increased in Alzheimer's disease, and microglial activation correlates with cognition, while amyloid load does not correlate with cognition. https://www.imperial.nhs.uk/consultant-directory/paul-edison
Remember, Leronlimab crosses the blood brain barrier. Microglial cells contain CCR5. Therefore LL will block the activation of microglial cells.
As in NASH, he will likely advise the employment of Brain MRI in determining Leronlimab effectiveness by measuring reduction in Alzheimer's plaques. It is now evaluating the relationship between neuroinflammation, tau, glucose metabolism, and structural and functional changes measured by MRI. He is evaluating novel microglial agents in mild cognitive impairment and Alzheimer's disease.
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Dr. Kabir Mody , from his linked in, " I am a dedicated, practicing clinical oncologist specializing in GI oncology, in particular hepatobiliary and pancreatic malignancies. I am focused on conducting meaningful, innovative, efficient and collaborative translational and clinical research in these malignancies. He is focused on fighting these cancers specifically and would like to "leverage the immune system" to do it.
From Wiki:, "VEGF-A has been implicated with poor prognosis in breast cancer. Numerous studies show a decreased overall survival and disease-free survival in those tumors overexpressing VEGF. The overexpression of VEGF-A may be an early step in the process of metastasis, a step that is involved in the "angiogenic" switch. Although VEGF-A has been correlated with poor survival, its exact mechanism of action in the progression of tumors remains unclear. "
From here: https://www.youtube.com/watch?v=uxkc6Ql1C-U
Cancer's tend to recruit macrophages to encourage & progress tumor growth and metastasis by upregulating or overexpressing CCR5 on the surface of these "effected" macrophages. These "affected" macrophages then produce "VEGF", vascular endothelial growth factor, which in turn helps to create the blood supply to support angiogenesis and tumor growth. The "affected" macrophages promote tumor cell proliferation, endovascular migration and invasion into the blood stream where they can circulate within the body, (these become the CTC circulating tumor cells, representing degree of metastasis and degree of cancer progression) and metastasis is what kills 90% of cancer patients, not the original tumor. Normally, Natural Killer Cells should be attacking cancer cells, but because of the increased CCR5, TRegs disable the NKCs and the cancer cells are not attacked. Leronlimab interferes by blocking CCR5 preventing macrophages from exuding VEGF, preventing tumor cell proliferation, metastasis and circulating tumor cells and prevents the TRegs from disabling the Natural Killer Cells from killing tumor cells.
From here: https://breast-cancer-research.biomedcentral....21-01391-1
"Well known as an essential co-receptor for HIV, more recently, CCR5 has become strongly implicated in the progression of human cancer, in particular, metastatic cancer [13]. CCR5, a seven trans-membrane G-protein coupled receptor (GPCR), is normally expressed only in the immune system; however, CCR5 becomes overexpressed in several malignancies and is overexpressed in breast cancer [12, 13]. In the analysis of > 2200 breast cancer patients, > 50% of patient’s tumors were CCR5+. and > 95% of triple-negative breast cancer (TNBC) were CCR5+ [12]. Several characteristics of CCR5 suggest the receptor may be important in human breast cancer. CCR5 receptor levels correlate with poor prognosis in breast cancer [13,14,15]. CCR5 expression correlates well with increased tumor heterogeneity in breast cancer [16, 17]. Upon transformation of breast epithelial cells, the increased expression of CCR5 results in increased motility and homing behavior to metastatic sites [12, 13]. Furthermore, CCR5+ breast cancer epithelial cells have both enhanced tumor-initiating capacity and form mammospheres with greater efficiency in mice [13], a feature of cancer stem cells. Finally, ectopic CCR5 expression within cancer epithelial cells is sufficient to drive cancer cell metastasis [12]. "
" These studies extend prior studies by showing CCR5 inhibition both prevents metastasis and reduces the progression of established metastasis in vivo."
Remember the Basket Trial???
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Dr. Otto Yang , from here: https://bioscience.ucla.edu/people/otto-yang/
" In particular, Dr. Yang has studied the mechanisms of HIV suppression by HIV-specific CD8+ cytotoxic T lymphocytes (CTL), which kill infected cells by recognizing viral peptides. His laboratory has demonstrated that CTL are potent killers of virus-infected cells and suppress HIV-1 replication through both killing and release of antiviral cytokines. "
From his linked in, " I am a physician-scientist who has had a basic science laboratory funded by NIH to study cellular immunology and virology for over 20 years, with over 170 peer-reviewed scientific publications in the field. Most recently my group has added SARS-CoV-2 to our research topics, and I have been the PI of 7 clinical trials of treating severe COVID-19 at UCLA Medical Center. I also remain a clinician who sees general infectious disease patients. "
https://www.youtube.com/watch?v=sCMwoVYeRA0
CytoDyn may be looking at hand and face transplants as indications as these would be indications which would require the use of Leronlimab for life as it is a variation of "Graft vs. Host" disease.
Dr. Paul Edison , more than likely brought on board for the indication of Alzheimer's Disease and possibly epilepsy. His work in assessing microglial activation and amyloid load showed that both these are increased in Alzheimer's disease, and microglial activation correlates with cognition, while amyloid load does not correlate with cognition. https://www.imperial.nhs.uk/consultant-directory/paul-edison
Remember, Leronlimab crosses the blood brain barrier. Microglial cells contain CCR5. Therefore LL will block the activation of microglial cells.
As in NASH, he will likely advise the employment of Brain MRI in determining Leronlimab effectiveness by measuring reduction in Alzheimer's plaques. It is now evaluating the relationship between neuroinflammation, tau, glucose metabolism, and structural and functional changes measured by MRI. He is evaluating novel microglial agents in mild cognitive impairment and Alzheimer's disease.
//
Dr. Kabir Mody , from his linked in, " I am a dedicated, practicing clinical oncologist specializing in GI oncology, in particular hepatobiliary and pancreatic malignancies. I am focused on conducting meaningful, innovative, efficient and collaborative translational and clinical research in these malignancies. He is focused on fighting these cancers specifically and would like to "leverage the immune system" to do it.
From Wiki:, "VEGF-A has been implicated with poor prognosis in breast cancer. Numerous studies show a decreased overall survival and disease-free survival in those tumors overexpressing VEGF. The overexpression of VEGF-A may be an early step in the process of metastasis, a step that is involved in the "angiogenic" switch. Although VEGF-A has been correlated with poor survival, its exact mechanism of action in the progression of tumors remains unclear. "
From here: https://www.youtube.com/watch?v=uxkc6Ql1C-U
Cancer's tend to recruit macrophages to encourage & progress tumor growth and metastasis by upregulating or overexpressing CCR5 on the surface of these "effected" macrophages. These "affected" macrophages then produce "VEGF", vascular endothelial growth factor, which in turn helps to create the blood supply to support angiogenesis and tumor growth. The "affected" macrophages promote tumor cell proliferation, endovascular migration and invasion into the blood stream where they can circulate within the body, (these become the CTC circulating tumor cells, representing degree of metastasis and degree of cancer progression) and metastasis is what kills 90% of cancer patients, not the original tumor. Normally, Natural Killer Cells should be attacking cancer cells, but because of the increased CCR5, TRegs disable the NKCs and the cancer cells are not attacked. Leronlimab interferes by blocking CCR5 preventing macrophages from exuding VEGF, preventing tumor cell proliferation, metastasis and circulating tumor cells and prevents the TRegs from disabling the Natural Killer Cells from killing tumor cells.
From here: https://breast-cancer-research.biomedcentral....21-01391-1
"Well known as an essential co-receptor for HIV, more recently, CCR5 has become strongly implicated in the progression of human cancer, in particular, metastatic cancer [13]. CCR5, a seven trans-membrane G-protein coupled receptor (GPCR), is normally expressed only in the immune system; however, CCR5 becomes overexpressed in several malignancies and is overexpressed in breast cancer [12, 13]. In the analysis of > 2200 breast cancer patients, > 50% of patient’s tumors were CCR5+. and > 95% of triple-negative breast cancer (TNBC) were CCR5+ [12]. Several characteristics of CCR5 suggest the receptor may be important in human breast cancer. CCR5 receptor levels correlate with poor prognosis in breast cancer [13,14,15]. CCR5 expression correlates well with increased tumor heterogeneity in breast cancer [16, 17]. Upon transformation of breast epithelial cells, the increased expression of CCR5 results in increased motility and homing behavior to metastatic sites [12, 13]. Furthermore, CCR5+ breast cancer epithelial cells have both enhanced tumor-initiating capacity and form mammospheres with greater efficiency in mice [13], a feature of cancer stem cells. Finally, ectopic CCR5 expression within cancer epithelial cells is sufficient to drive cancer cell metastasis [12]. "
" These studies extend prior studies by showing CCR5 inhibition both prevents metastasis and reduces the progression of established metastasis in vivo."
Remember the Basket Trial???
//
Dr. Otto Yang , from here: https://bioscience.ucla.edu/people/otto-yang/
" In particular, Dr. Yang has studied the mechanisms of HIV suppression by HIV-specific CD8+ cytotoxic T lymphocytes (CTL), which kill infected cells by recognizing viral peptides. His laboratory has demonstrated that CTL are potent killers of virus-infected cells and suppress HIV-1 replication through both killing and release of antiviral cytokines. "
From his linked in, " I am a physician-scientist who has had a basic science laboratory funded by NIH to study cellular immunology and virology for over 20 years, with over 170 peer-reviewed scientific publications in the field. Most recently my group has added SARS-CoV-2 to our research topics, and I have been the PI of 7 clinical trials of treating severe COVID-19 at UCLA Medical Center. I also remain a clinician who sees general infectious disease patients. "
https://www.youtube.com/watch?v=sCMwoVYeRA0
CytoDyn may be looking at hand and face transplants as indications as these would be indications which would require the use of Leronlimab for life as it is a variation of "Graft vs. Host" disease.
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