title: An overview of novel therapies for acute hereditary angioedema.
abstract: Hereditary angioedema is an episodic swelling disorder with autosomal dominant inheritance. Attacks are characterized by nonpitting edema of external or mucosal body surfaces. Patients often present with swelling of the extremities, abdominal pain, and swelling of the mouth and throat, which can at times lead to asphyxiation. The disease is caused by a mutation in the gene encoding the complement C1-inhibitor protein, which leads to unregulated production of bradykinin. Long-term therapy has depended on the use of attenuated androgens or plasmin inhibitors but in the US there was, until recently, no specific therapy for acute attacks. As well, many patients with hereditary angioedema in the US were either not adequately controlled on previously available therapies or required doses of medications that exposed them to the risk of serious adverse effects. Five companies have completed or are currently conducting phase III clinical trials in the development of specific therapies to terminate acute attacks or to be used as prophylaxis. These products are based on either replacement therapy with purified plasma-derived or recombinant C1-inhibitor, or inhibition of the kinin-generating pathways with a recombinant plasma kallikrein inhibitor or bradykinin type 2 receptor antagonist. Published studies thus far suggest that all of these products are likely to be effective. These new therapies will likely lead to a totally new approach in treating hereditary angioedema.
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: Firszt
authors.forename: Michael M
authors.initials: MM
authors.lastname: Frank
mesh_terms: D000208:Acute Disease; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000728:Androgens / Q000627:therapeutic use*; D000933:Antifibrinolytic Agents / Q000627:therapeutic use*; D001920:Bradykinin / Q000031:analogs & derivatives / Q000627:therapeutic use; D065168:Bradykinin Receptor Antagonists; D050718:Complement C1 Inhibitor Protein / Q000378:metabolism / Q000627:therapeutic use; D003613:Danazol / Q000627:therapeutic use; D056828:Hereditary Angioedema Type III / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D056829:Hereditary Angioedema Types I and II / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006727:Hormone Antagonists / Q000627:therapeutic use*; D006801:Humans; D007610:Kallikreins / Q000037:antagonists & inhibitors; D010455:Peptides / Q000627:therapeutic use; D014148:Tranexamic Acid / Q000627:therapeutic use
chemical_list: D000319:Adrenergic beta-Antagonists; D000728:Androgens; D000933:Antifibrinolytic Agents; D065168:Bradykinin Receptor Antagonists; D050718:Complement C1 Inhibitor Protein; D006727:Hormone Antagonists; D010455:Peptides; C511194:ecallantide; D014148:Tranexamic Acid; C065679:icatibant; D007610:Kallikreins; D003613:Danazol; D001920:Bradykinin