Nov 10, 2011 · We demonstrate that selective reduction of prekallikrein (PKK), another member of the contact system, using antisense oligonucleotide (ASO) technology results in an antithrombotic phenotype in mice. The effects of PKK deficiency were compared with those of fXII deficiency produced by specific ASO-mediated reduction of fXII.

Jan 31, 2019 · In addition to serving as a critical component of the intrinsic pathway, FXII is also a central component of the contact system that includes PKK (prekallikrein) and HK (high molecular weight kininogen). Activation of the intrinsic pathway …

Activation of FXII results from a conformational change induced by binding ("contact") with negatively charged surfaces. The activated serine protease FXIIa drives both the proinflammatory kallikrein-kinin pathway and the procoagulant intrinsic coagulation cascade, respectively.

Introduction: The contact system proteins factor XII (FXII), prekallikrein (PK) and high molecular weight kininogen (HK) have roles in coagulation, fibrinolysis, thrombin-induced platelet activation, cell adhesion and angeogenisis. It has been suggested that inherited or acquired deficiencies of these proteins may be risk factors for thrombosis.

IONIS-PKK Rx is a second-generation 2'-O-(2-methoxyethyl)-modified chimeric antisense oligonucleotide, designed to bind and selectively reduce prekallikrein (PKK) mRNA in the liver.

Sep 2, 2020 · In a compassionate-use pilot study, two patients with severe bradykinin-mediated angioedema were initially administered weekly subcutaneous injections of the unconjugated parent drug, IONIS-PKK...

Feb 28, 2019 · IONIS-PKKRx is a second-generation 2'-O- (2-methoxyethyl)-modified chimeric antisense oligonucleotide, designed to bind and selectively reduce prekallikrein (PKK) mRNA in the liver.

dysregulation of the contact system leading to recurrent, sometimes fatal, angioedema attacks. IONIS-PKK Rx is a second-generation 2¢-O-(2-methoxyethyl)-modified chimeric antisense oligonucleotide, designed to bind and selectively reduce prekallikrein (PKK) mRNA in the liver. IONIS-PKK Rx demonstrated dose-dependent re-

Dec 1, 2015 · The results support the concept that fXII and PKK play important and perhaps nonredundant roles in pathogenic thrombus propagation, and highlight a novel, specific and safe pharmaceutical approach to target these contact system proteases.

Nov 1, 2001 · As shown in Table 2, MNU increased the frequencies for mutation in FX-11-pKK in a dose-dependent manner. At a concentration of 2.5 mM, GlnV o tRNA suppressor mutations comprised 85% of the total mutations recovered, giving a mutation frequency of 1×10 −5 .