Question

Mention new complement inhibitors used in treatment of paroxysmal nocturnal hemoglobinuria (PNH).

Hint:

Eculizumab and ravulizumab are the main complement inhibitors used in PNH, with ravulizumab offering a longer duration of action and fewer infusions.

Answer 1

Step 1: Overview of Paroxysmal Nocturnal Hemoglobinuria (PNH).
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematologic disorder characterized by hemolysis, thrombosis, and bone marrow failure. PNH is caused by a mutation in the PIGA gene, which affects the expression of complement-regulatory proteins on the surface of red blood cells, leading to uncontrolled complement activation and hemolysis.

Step 2: Complement Inhibitors in PNH.
1. Eculizumab: Eculizumab is a monoclonal antibody that inhibits the complement protein C5, preventing its cleavage into C5a and C5b, which are involved in the formation of the membrane attack complex (MAC) that damages red blood cells in PNH. It is the standard treatment for PNH and reduces hemolysis and associated complications.
2. Ravulizumab: Ravulizumab is a newer, longer-acting complement inhibitor that also targets C5. It is similar to eculizumab but has a prolonged half-life, allowing for less frequent dosing (every 8 weeks). It has been shown to be equally effective as eculizumab in treating PNH, with fewer infusions required.
3. Coversin: Coversin is a novel complement inhibitor that targets C5, similar to eculizumab, but it is a smaller peptide and is being studied for its potential in treating PNH and other complement-mediated disorders. It is still under investigation but shows promise in early trials.