Rolul Hepcidinei in Anemia din bolile cronice o abordare translationala. Grigoras Adelina Grigorescu Beatrice-Adriana Hluscu Otilia

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1 Rolul Hepcidinei in Anemia din bolile cronice o abordare translationala Grigoras Adelina Grigorescu Beatrice-Adriana Hluscu Otilia

2 Anemia din bolile cronice definitii, cauze ACD anemia cu a doua rata de prevalenta la nivel mondial, se intalneste in randul pacientilor cu activare imuna acuta sau cronica Cunoscuta si sub denumirea de anemie din cadrul inflamatiilor

3 Anemia din bolile cronice Hp intra in actiune Date recente sugereaza ca Helicobacter pylori, un agent infectios comun al tubului digestiv, este asociat cu deficit de fier si anemie. Hp ar putea fi cea mai frecventa infectie bacteriana la nivel mondial infectand aproximativ jumatate din populatia din tarile dezvoltate si 80 din populatia din tarile in curs de dezvoltare. Infectia cu H. pylori este puternic asociata cu ulcerul peptic si cancerul gastric. Cateva studii transversale au demonstrat o asociere semnificativa intre infectia cu H. pylori si rezervele scazute de fier, anemia feripriva si de asemenea un raspuns slab la terapia de substitutie cu fier. Cardenas VM, Mulla ZD, Ortiz M, Graham DY, Iron deficiency and Helicobacter pylori infection in the United States. Am J Epidemiol 163:

4 Caile majore ale transferului fierului intre celule si tesuturi Hentze... Andrews, Cell 117: 285 (2004)

5 Caile majore ale transferului fierului intre celule si tesuturi X X Cai blocate in anemia din bolile cronice Hentze... Andrews, Cell 117: 285 (2004)

6 Hentze... Andrews, Cell 117: 285 (2004)

7

8 ~2-4 nm NMR solution structure (2002)

9 Supraexprimarea transgenica sau constitutiva a genei hepcidinei duce la anemie severa prin deficit de fier la soarece. Inflamatia la soareci care sunt hepcidin-deficienti nu a dus la deficit de fier, o constatare care sugereaza ca hepcidina pare sa aiba o pozitie centrala in dirijarea circuitului fierului prin scaderea absorbtiei duodenale si in blocarea eliberarii fierului de la nivelul macrofagelor procese care se observa in anemia din bolile cronice Bobby J. Cherayil, Shiri Ellenbogen, Nandakumar N. Shanmugam. (2011) Iron and intestinal immunity. Current Opinion in Gastroenterology. E. Galesloot, S. H. Vermeulen, A. J. Geurts-Moespot, S. M. Klaver, J. J. Kroot, D. van Tienoven, J. F. M. Wetzels, L. A. L. M. Kiemeney, F. C. Sweep, M. den Heijer, D. W. Swinkels. (2011) Serum hepcidin: reference ranges and biochemical correlates in the general population. Blood 117:25, e218-e225

10 Hepcidina si anemia din bolile cronice Hepcidina pare sa blocheze preluarea fierului de la nivelul duodenului si eliberarea lui de la nivelul Macrofagelor (SRE), prin urmare scazand livrarea de Fe catre precursorii eritroizi Un antagonist al hepcidinei s-ar putea dovedi folositor pentru pacientii cu anemie din bolile cronice Nivelele urinare inalte de hepcidina posibil marker de diagnostic pentru anemia din bolile cronice

11 Calea nefericita We ve got a new wonder drug! we give it to you and wonder what it will do

12 Conceptul de Farmacologie Translationala Ramura a cercetarii medicale care isi propune sa conecteze intr-un mod direct cercetarea fundamentala cu ingrijirea pacientului Cercetare medicala orientata inspre boala De la mecanism molecular la aplicatie clinica

13 Freising, Germany, May 23, 2011 Pieris AG announced today preclinical in vitro and in vivo data for its PRS-080 Anticalin antagonist program targeting hepcidin, a small peptide which plays a pivotal role in the regulation of iron levels in the blood. PRS-080 showcases Anticalins ability to encapsulate small targets like hepcidin with high specificity and potency. The results of Pieris PRS-080 studies are being presented at the International BioIron Society Meeting being held May in Vancouver, Canada in an oral presentation entitled Exploiting lipocalin biochemistry for the treatment of anemia: discovery and characterization of an anti-hepcidin therapeutic.

14 In God we trust, all others must bring data. J. Newhouse

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