Complement Blockers

(rINNM)
Synonyms: Inhibidores del complemento.
Cyrillic synonym: Блокаторы Комплемента.

Profile

Complement is a group of plasma and cellular proteins contributing to the innate immune system and is so called because it complements the microbicidal action of antibodies. The complement system is activated by the antigen-antibody complex followed by a cascade reaction of complement proteins culminating in microbial cell lysis. Complement also plays a part in many other physiological processes and regulatory mechanisms are in place to prevent inflammatory damage to host tissues through the inappropriate activation of complement. Hereditary or acquired abnormalities of the complement system are associated with a variety of disorders depending on which part of the system is affected, and include recurrent infections, partial lipodystrophy, hereditary angioedema, paroxysmal nocturnal haemoglobinuria, non-specific vasculitis, glomerulonephritis, cardiovascular disease, rheumatoid arthritis, sepsis, asthma, acute respiratory distress syndrome, psoriasis, SLE, bullous pemphigoid, discoid lupus, and graft survival after solid organ transplantation. A number of substances are used or are under investigation for their ability to block activation of the complement system:
complement C1 esterase inhibitor is given as replacement therapy in the treatment of hereditary angioedema
eculizumab is a monoclonal antibody that targets the terminal C5 protein of complement and is given in the treatment of paroxysmal nocturnal haemoglobinuria
pexelizumab is a similar substance under investigation in patients undergoing coronary artery revascularisation procedures
mirococept (APT-070, SCR1-3) is a derivative of soluble complement receptor type 1 (SCR1) under investigation for the prevention of post transplantation graft dysfunction
TP-10, a form of SCR1 has also been investigated for respiratory disorders
myristoylated-peptidyl-recombinant human CD59 is under investigation for paroxysmal nocturnal haemoglobinuria
1. Bhole D, Stahl GL. Therapeutic potential of targeting the complement cascade in critical care medicine. Crit Care Med 2003; 31 (suppl): S97–S104
2. Brook E, et al. Opportunities for new therapies based on the natural regulators of complement activation. Ann N Y Acad Sci 2005; 1056: 176–88.
Published May 04, 2019.