Coronavirus (COVID-19) Therapeutic Treatment: The Potential of Lenzilumab | Cytokine Storms
Discussion about a very exciting new drug called Lenzilumab by the biotech company, Humanigen which is currently in FDA phase 3 (coronavirus) COVID-19 trials. Lenzilumab is a monoclonal antibody against granulocyte macrophage colony stimulating factor or GM-CSF. in a 12 patient study at the Mayo Clinic, treatment with lenzilumab showed promise in patients with severe and critical COVID-19 pneumonia.
It is important to understand this progression because while the symptoms of the early phase are due to the virus, the later phases are immunological driven by the cytokine storms. As I have talked about in previous videos, cytokines are messenger proteins made by the immune cells to coordinate immune responses. For an unknown reason, some people are more susceptible to these cytokine storms which can be described as a hyper immune response to the virus. These cytokine storms have been implicated in acute respiratory distress syndrome, cardiac, liver and kidney damage along with strokes and blood clots.
So that is why in the early phase of the COVID-19, antivirals like hydroxychloroquine and remdesivir have shown some promise, but in the later phases, they haven’t because it is the cytokines and the cytokine storms causing the pathology and mortality. This is why there have been a focus on therapeutics to quell these storms and regulate the immune system.
The cytokine pathways are very complex and identifying the main cytokines involved is the biggest challenge doctors and scientists are facing. As I have discussed in previous videos about Dr. Bruce Patterson’s research identifying the chemokine, RANTES, as the main cytokine involved in these storms, the researchers at Humanigen have identified another key cytokine responsible for the immunological damage in COVID-19: granulocyte macrophage colony stimulating factor or GM-CSF.
GM-CSF is a myelopoietic growth factor and pro-inflammatory cytokine and plays a critical role in alveolar macrophage homeostasis, lung inflammation and immunological disease and it believed lenzilumab blocks this cytokine thus potentially quelling the cytokine storm.
GM-CSF is a cytokine and an important hematopoietic growth factor and immune modulator and plays a key role in the differentiation and proliferation of monocytes, macrophages, granulocytes and elevated GM-CSF levels are associated with autoimmune and inflammatory diseases and cancer.
GM-CSF has been described as
a communication conduit between tissue-invading lymphocytes and myeloid cells.
Even though lymphocytes are in all likelihood the instigators of chronic inflammatory disease, GM-CSF-activated phagocytes are well equipped to cause tissue damage.
It is theorized by some that in COVID-19, GM-CSF dysregulation induces an overactivation of myeloid cells that secrete pro-inflammatory cytokines and chemokines that infiltrate and destroy lung, heart and nervous system tissues.
Lenzilumab is a recombinant monoclonal antibody that works by binding and neutralizing GM-CSF to prevent it from binding to the GM-CSF receptor. By preventing GM-CSF from binding to its receptor, lenzilumab blocks the signal to myeloid progenitor cells.
What are Cytokine Storms?:
Dr. Patterson’s Discussion:
Post Infection Complications:
Leronlimab Video:
