Vesna Grivcheva-Panovska

University Saints Cyril and Methodius
Macedonia

Title: Innovative therapeutic approach of hereditary angioedema

Biography

Abstract

Hereditary angioedema (HAE) is a rare genetic, life-threatening disease. Patients affected by HAE most of the time are without visible signs of the disease, besides the attacks, which can be brutal, painful and lethal. Several therapeutic approaches have been developed and used with various success, recombinant human C1INH (rhC1INH) being the most innovative current approach. Recombinant human C1INH is a purified derivative from rabbit milk which expresses the gene that encodes the synthesis of C1INH. The amino acid sequence of the recombinant form is identical to the human C1INH. C1INH is single-chain plasma glycoprotein with a molecular mass of 73,650 belonging to the super-family of serine protease inhibitors in plasma. C1INH is the only known inhibitor of activated plasma subcomponents C1s and C1r of the complementary component 1 of the complementary cascade classical pathway. Furthermore, C1INH inhibits the Manan-associated serine protease 2 (MASP2) of the lectin pathway of the complement. Additionally, it is the main inhibitor of the activated factor XII, factor XI and kallikrein of the plasma contact system. The rhC1INH was primarily developed for treatment of acute angioedema attacks in patients with HAE due to C1INH activity deficiency. The rhC1INH inhibitory potential of target proteases C1s, kallikrein, factor XIa and factor XIIa is highly comparable to the endogenous human C1 esterase inhibitory potential in vitro. Additional data of the efficacy are obtained by multiple analysis of primary efficacy sensitivity end point as well as the results of secondary and explorative efficacy.