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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Khrenov, A. Articles by Saenko, E. Search for Related Content PubMed Articles by Khrenov, A. Articles by Saenko, E. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 August 2003, Vol. 102, No. 3, pp. 777 Peptide decoys: cure for FVIII inhibitors? Hemophilia A is a genetic disorder characterized by a deficient factor VIII (FVIII) activity. Among patients receiving FVIII replacement therapy, a significant number develop antibodies inhibiting FVIII procoagulant activity (called inhibitors). Development of inhibitors severely complicates the course of the disease, dramatically decreasing the efficacy of FVIII replacement therapy. The problem of inhibitors is one of the most complex in hemophilia A treatment, because a great variety of inhibitors directed against different epitopes in the FVIII molecule is found in individual patients. At present, there is no effective solution for this problem, and any developments in this area are greatly appreciated by clinicians. The novel study by Villard and colleagues in this issue (page 949) appears promising, as it demonstrates that peptide surrogates, mimicking epitopes recognized by inhibitors, may block their inhibitory activity, thereby allowing restoration of a normal procoagulant activity of FVIII. To prove their concept, Villard et al used the human monoclonal inhibitory antibody Bo2C11 specific for the C2 domain of FVIII as a model for inhibitors. The authors showed that selected dodecapeptides neutralized the Bo2C11 inhibitory activity in the functional test. Moreover, these peptides were efficient in preventing inhibition of FVIII activity by Bo2C11 in a murine FVIII-knockout model of hemophilia A, suggesting that peptide decoys may also be used in vivo. Remarkably, the phage display technology used by the authors allowed selection of peptides that lack sequence homology with FVIII and therefore do not interfere with FVIII function. But a number of issues should be addressed in order to evaluate the potential of peptide decoys for hemophilia A treatment: peptide half-life in vivo should be improved; the polyclonal nature of inhibitors and differences in inhibitors spectra among patients require designing mixtures of peptides which mimic different FVIII epitopes. In summary, the study of Villard et al outlines a novel approach to the solution of inhibitor problems in hemophilia A. Alexey Khrenov, and Evgueni Saenko American Red Cross CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Peptide decoys selected by phage display block in vitro and in vivo activity of a human anti-FVIII inhibitor Sylvie Villard, Sébastien Lacroix-Desmazes, Thomas Kieber-Emmons, Dominique Piquer, Sabrina Grailly, Abdellah Benhida, Srini V. Kaveri, Jean-Marie Saint-Remy, and Claude Granier Blood 2003 102: 949-952. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Khrenov, A. Articles by Saenko, E. Search for Related Content PubMed Articles by Khrenov, A. Articles by Saenko, E. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?

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