Replacement Therapy in Hereditary Angioedema

Abstract

Although considerable progress has been made during the past two decades in the use of androgens to prevent attacks of hereditary angioedema, replacement of the deficient C1-inhibitor protein would provide a useful menas of treatment once an attack has begun. We studied the clinical use of C1 inhibitor that was partly purified on a large scale from pooled plasma. The in vivo efficacy and safety of this protein concentrate were evaluated during 11 intravenous infusions in eight patients with hereditary angioedema. Three patients received the C1-inhibitor preparation during an asymptomatic period. Increases in serum C4 activity provided evidence of the biologic activity of the infused inhibitor. Intravenous administration of the concentrate during acute abdominal or laryngeal attacks of hereditary angioedema in five patients resulted in abatement of symptoms in addition to increased serum C4 activity. No untoward effects of the intravenous administration of the C1 inhibitor were observed in these eight patients. Thus, this C1-inhibitor preparation seems to offer the potential for safe, effective replacement therapy and may provide a means of controlling an attack of hereditary angioedema that is in progress.

Recombinant and Plasma-Purified Human C1 Inhibitor for the Treatment of Hereditary Angioedema

“…All of these groups already had facilities for collecting and pooling plasma from thousands of donors and purifying individual plasma proteins because all were suppliers of gamma globulin for patient use. The author's own group had access to the American Red Cross preparation and in 1980 reported that C1 inhibitor infusion raised plasma C1 inhibitor levels as expected in 8 patients and, as a consequence of its action in inhibiting activated C1, also raised the levels of serum C4[14]. We reported that this treatment terminated angioedema attacks in 5 of our patients who were having attacks at the time of their infusion[14].…”

“…The author's own group had access to the American Red Cross preparation and in 1980 reported that C1 inhibitor infusion raised plasma C1 inhibitor levels as expected in 8 patients and, as a consequence of its action in inhibiting activated C1, also raised the levels of serum C4[14]. We reported that this treatment terminated angioedema attacks in 5 of our patients who were having attacks at the time of their infusion[14]. At about the same time, the Dutch Red Cross developed a preparation of C1 inhibitor, and Agostoni et al reported that it was effective in terminating attacks of angioedema[15].…”

The Mammalian Innate Immune System: Potential Targets for Drug Development

“…The C1 inhibitor protein and monoclonal antibodies directed against mannose binding lectin have been used to inhibit the pathogen detection step [125][126][127]. The natural inhibitor of complement, complement receptor 1 (CR1) found on the surface of some innate immune cells, causes the disassembly of C3 and C5 convertases and inactivation of C3b and C4b [128,129].…”

A Sensitive Specific Hemolytic Assay for Proenzyme C1

“…C1 inhibitor was isolated from human serum by the method of Prograis et al [31]. A crude but functionally active Cl inhibitor preparation free of Cl was prepared by a modification of the procedure of Gadek et al [14]. For the latter procedure (personal communication, Dr. Carl Hammer, NIAID, NIH, Bethesda, Md., USA), 20 mg of polyethylene glycol 6000 (PEG) was added to 200 p.1 of fresh serum, incu bated 15 min on ice, and centrifuged at 4 0 C for 15 min at 3,000 rpm.…”