Icatibant- Bradykinin Blockers- Might Reduce the Need for Ventilators

Bradykinin-Receptor Antagonist for COVID-19 Treatment. Bradykinin is a peptide that promotes inflammation, which in excess may cause the fluid build-up in the lungs of patients with COVID-19 infections. A biologist at Oak Ridge National Laboratory in Tennessee found the expression of genes for key enzymes in the renin-angiotensin system (RAS), involved in blood pressure regulation and fluid balance. It was found that the kinin system, a key peptide- bradykinin, causes blood vessels to leak and fluid to accumulate in tissues and organs, was out of balance in COVID-19 patients. Infected patients showed a high expression of genes for the bradykinin receptors and enzymes called kallikreins that activate the kinin pathway. Angiotensin-converting enzyme-2 (ACE2) is a key enzyme in the RAS- the SARS-CoV-2 receptor, which regulates the kinin system, connecting the dots. This hypothesized that a dysregulated bradykinin system led to leaky blood vessels in the lungs, causing excess fluid to build up lends support, but further confirmation is needed. As there are already a couple of approved drugs that can interfere with the kinin pathway, they have begun deploying them in several clinical trials How this works? The RAS pathway controls the kinin system ACE breaks down bradykinin and ACE2 breaks down DABK ACE2 combines with SARS/ SARS-CoV-2 and internalized into the cell during infection Extracellular levels of the enzyme thus drop, and bradykinin cascade goes into overdrive Targeting bradykinin pathway in COVID Currently, there are two drugs approved that target the kinin system: Icatibant (a B2R blocker) Monoclonal antibody- lanadelumab, which inhibits plasma kallikrein This study suggests that targeting the kinin system early in the disease, which hasn’t yet developed ARDS, might help. However, COVID-19 patients taking icatibant showed marked improvement in oxygen levels and decreased need for supplemental oxygen. This preliminary observation supports the idea that icatibant might help treat COVID and should, therefore, be studied in a double-blind placebo-controlled fashion in COVID patients. Clinical trials in process: - A randomized clinical trial in the US is testing icatibant in critically ill COVID-19 patients. - A clinical trial in Cleveland is testing lanadelumab in COVID-19 patients with pneumonia. - A clinical trial in the Netherlands is testing the plasma kallikrein inhibitor in hospitalized COVID-19 patients receiving supplemental oxygen. - A study (Van de Veerdonk & team) is currently setting up mass spectrometry to measure kinins in the plasma, which have a very short half-life. - Testing ACE2 as a treatment for lung failure is in a Phase 2 trial in COVID-19 patients. Now it’s up to the physicians to connect the dots. How far is this helpful?

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Dear dr Prashant ved It will be great break through in treatment of covid infection though still it is a hypothesis and under trial but it will bring a sea change in line of treatment Thanx for sharing

Thank you doctor
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Great

Thank you doctor
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