Genetically engineering botulinum toxin could help advance new treatments for everything from neurodegenerative disorders to cytokine storms.
Using electroacupuncture, researchers stimulated the vagus-adrenal axis to induce secretion of dopamine from chromaffin cells in the adrenal glands. Mice exposed to this treatment had lower levels of three types of inflammation-inducing cytokines and improved survival chances over those who did not receive electroacupuncture. Animals treated with the method immediately before they developed cytokine storms experienced lower levels of inflammation during their disease and an increase in survival odds from 20% to 80%.
After natural killer immune cells kill virus-infected cells, T and B immune cells produce cytokines. This makes the immune reaction stronger and results in the cytokine storm associated with severe COVID-19 infection.
Treating coronavirus patients with alpha-blockers may help prevent the cytokine storm associated with severe COVID-19 infection. Alpha-blockers interfere with the cell signaling that triggers cytokine storms. Mice with bacterial infections that were treated with alpha-blockers experienced reduced cytokine storms and decreased death rates.
SARS-CoV-2, the virus responsible for COVID-19, enters human cells by attaching to ACE2 and utilizing TMPRSS2. Drugs that block ACE2 or inhibit the enzyme could help treat the coronavirus, but only during early infection. As the infection progresses, SARS-CoV-2 becomes engulfed in human cells, reducing the number of ACE2 receptors on a cell and leading to an increase of angiotensin II in the blood. Angiotensin II triggers an inflammatory pathway, providing a positive feedback cycle, named IL-6 amplifier, resulting in excessive immune activation and the cytokine storm associated with severe COVID-19.
UCSD has launched a Phase III clinical trial to assess whether tocilizumab (Actemra), a drug commonly prescribed for rheumatoid arthritis and other inflammatory disorders, has therapeutic value for those at risk of developing severe COVID-19 infection. The drug is a monoclonal antibody-based therapy that blocks receptors for interleukin-6, a cytokine that triggers inflammation as an early immune response to coronavirus. Blocking IL-6 could prevent the risk of the COVID-19 associated cytokine storm many with severe infection experience.
A new clinical trial is underway to test ibudilast, an asthma drug approved in Japan, for the treatment of severe COVID-19. Ibudilast is a MIF inhibitor. MIF is a gene that regulates immune response and is a driver of inflammation which results in the cytokine storm associated with coronavirus.
Researchers have designed antibody-like receptor proteins that can bind to cytokines, possibly reducing the effects of the COVID-19 associated cytokine storm.
