Development and Characterization of an Anti-FXIIa Monoclonal Antibody for the Treatment of Hereditary Angioedema

Cao, Zhang; Biondo, Mark; Rayzman, Veronika; Hardy, Matthew P.; McDonald, Anne; Busfield, Samantha J.; Nolte, Marc W.; Wilson, Michael; Nash, Andrew D.; Panousis, Con

doi:10.1016/j.jaci.2014.12.1570

Cited by 16 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The beneficial effects of rHA-Infestin-4 in tMCAO observed in our study are most likely due to the antithrombotic and anti-inflammatory properties of FXIIa inhibition [ 20 , 44 , 52 , 53 ]. Anti-inflammatory effects of rHA-Infestin-4 application could be demonstrated in this study by reduction of edema formation in infarcted brain tissue as well as in another study applying rHA-Infestin-4 in a murine traumatic brain injury model [ 54 ], whereas antithrombotic effects of rHA-Infestin-4 have been reported in several thrombosis models [ 26 ].…”

Section: Discussionmentioning

confidence: 93%

The Coagulation Factor XIIa Inhibitor rHA-Infestin-4 Improves Outcome after Cerebral Ischemia/Reperfusion Injury in Rats

et al. 2016

Self Cite

View full text Add to dashboard Cite

Background and PurposeIschemic stroke provokes severe brain damage and remains a predominant disease in industrialized countries. The coagulation factor XII (FXII)-driven contact activation system plays a central, but not yet fully defined pathogenic role in stroke development. Here, we investigated the efficacy of the FXIIa inhibitor rHA-Infestin-4 in a rat model of ischemic stroke using both a prophylactic and a therapeutic approach.MethodsFor prophylactic treatment, animals were treated intravenously with 100 mg/kg rHA-Infestin-4 or an equal volume of saline 15 min prior to transient middle cerebral artery occlusion (tMCAO) of 90 min. For therapeutic treatment, 100 mg/kg rHA-Infestin-4, or an equal volume of saline, was administered directly after the start of reperfusion. At 24 h after tMCAO, rats were tested for neurological deficits and blood was drawn for coagulation assays. Finally, brains were removed and analyzed for infarct area and edema formation.ResultsWithin prophylactic rHA-Infestin-4 treatment, infarct areas and brain edema formation were reduced accompanied by better neurological scores and survival compared to controls. Following therapeutic treatment, neurological outcome and survival were still improved although overall effects were less pronounced compared to prophylaxis.ConclusionsWith regard to the central role of the FXII-driven contact activation system in ischemic stroke, inhibition of FXIIa may represent a new and promising treatment approach to prevent cerebral ischemia/reperfusion injury.

show abstract

Section: Discussionmentioning

confidence: 93%

The Coagulation Factor XIIa Inhibitor rHA-Infestin-4 Improves Outcome after Cerebral Ischemia/Reperfusion Injury in Rats

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Preliminary data was presented at the AAAAI conference in February 2015. 23 The initial compound, 3F7, selected from a human phage display antibody library, was shown to be a potent and specific inhibitor of Factor XIIa in enzymatic studies with binding capability to rabbit, mouse, and human activated Factor XII. Murine models have demonstrated attenuation of contact-system induced skin edema with 3F7 administration.…”

Section: Emerging Therapies For Long Term Prophylaxismentioning

confidence: 99%

Emerging Therapies in Hereditary Angioedema

Meng

Riedl

2017

Immunology and Allergy Clinics of North America

View full text Add to dashboard Cite

SYNOPSIS Remarkable progress has been made in the treatment of bradykinin mediated angioedema with the advent of multiple new angioedema specific therapies over the last decade, largely studied in patients with hereditary angioedema (HAE) due to C1 esterase inhibitor (C1-INH) deficiency. While affected individuals previously had little treatment available, patients in many parts of the world now have effective medications available for prophylaxis and treatment of acute angioedema attacks. Despite these advances, patients are still faced with challenges of a burdensome disease that can lead to debilitating and dangerous angioedema episodes associated with significant costs for individuals and society. The burden of treatment must also be addressed with regard to medication administration difficulties, treatment complications, and adverse side effects. Multiple new therapies with novel mechanisms of action are currently being investigated and may offer potential solutions to these challenges faced by patients and physicians. We herein review the emerging therapeutic options for the treatment of HAE.

show abstract

“…Dyax is evaluating a human antibody against kallikrein (DX2930), which only has to be administered once or twice per month due to its long half‐life . CSL recently presented the monoclonal antibody CSL312, which binds to factor XIIa and thus inhibits activation of the contact system and subsequent bradykinin formation .…”

Section: Discussionmentioning

confidence: 99%

Prophylaxis in hereditary angioedema (HAE) with C1 inhibitor deficiency

Greve

Straßen

Gorczyza

et al. 2016

J Deutsche Derma Gesell

View full text Add to dashboard Cite

SummaryHereditary angioedema (HAE) is a rare congenital disorder characterized by recurrent episodes of subcutaneous or submucosal edema. Laryngeal manifestations can be life-threatening. In the majority of cases, the disease can be adequately treated with an on-demand approach -in some cases, however, short-or long-term prophylaxis is indicated. Attenuated androgens used to be the drugs of choice, but they are associated with considerable side effects and no longer commercially available in the German-speaking countries of the EU. They are currently being replaced by more effective and more tolerable agents such C1-inhibitors, the kallikrein inhibitor ecallantide, and the B2 receptor antagonist icatibant, which have recently obtained market authorization. These new drugs have had a major impact, especially on the indications and procedures for long-term prophylaxis. According to the most recent international consensus papers and our own experience, self-administered C1-inhibitors are now the first option for long-term prophylactic therapy. The decision for prophylaxis should no longer be based on single parameters such as the frequency of attacks but on adequate overall disease control including quality of life. More drugs are currently being developed, which may lead to further changes in the treatment algorithms of HAE.

show abstract

Development and Characterization of an Anti-FXIIa Monoclonal Antibody for the Treatment of Hereditary Angioedema

Cited by 16 publications

References 0 publications

The Coagulation Factor XIIa Inhibitor rHA-Infestin-4 Improves Outcome after Cerebral Ischemia/Reperfusion Injury in Rats

The Coagulation Factor XIIa Inhibitor rHA-Infestin-4 Improves Outcome after Cerebral Ischemia/Reperfusion Injury in Rats

Emerging Therapies in Hereditary Angioedema

Prophylaxis in hereditary angioedema (HAE) with C1 inhibitor deficiency

Contact Info

Product

Resources

About