Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 9 July 2004:
Vol. 305. no. 5681, pp. 239 - 242
DOI: 10.1126/science.1098313
Prev | Table of Contents | Next

Reports

Derivatives of Erythropoietin That Are Tissue Protective But Not Erythropoietic

Marcel Leist,1* Pietro Ghezzi,2,3* Giovanni Grasso,3,4 Roberto Bianchi,2 Pia Villa,2,5 Maddalena Fratelli,2 Costanza Savino,2 Marina Bianchi,2 Jacob Nielsen,1 Jens Gerwien,1 Pekka Kallunki,1 Anna Kirstine Larsen,1 Lone Helboe,1 Søren Christensen,1 Lars O. Pedersen,1 Mette Nielsen,1 Lars Torup,1 Thomas Sager,1 Alessandra Sfacteria,3,4 Serhat Erbayraktar,3,6 Zubeyde Erbayraktar,3,6 Necati Gokmen,6 Osman Yilmaz,3,6 Carla Cerami-Hand,3,7 Qiao-wen Xie,3,7 Thomas Coleman,3,7 Anthony Cerami,3,7{dagger} Michael Brines3,7

Erythropoietin (EPO) is both hematopoietic and tissue protective, putatively through interaction with different receptors. We generated receptor subtype–selective ligands allowing the separation of EPO's bioactivities at the cellular level and in animals. Carbamylated EPO (CEPO) or certain EPO mutants did not bind to the classical EPO receptor (EPOR) and did not show any hematopoietic activity in human cell signaling assays or upon chronic dosing in different animal species. Nevertheless, CEPO and various nonhematopoietic mutants were cytoprotective in vitro and conferred neuroprotection against stroke, spinal cord compression, diabetic neuropathy, and experimental autoimmune encephalomyelitis at a potency and efficacy comparable to EPO.

1 H. Lundbeck A/S, 2500 Valby, Denmark.
2 Mario Negri Institute of Pharmacological Research, 20157 Milano, Italy.
3 The Kenneth S. Warren Institute, Ossining, NY 10562, USA.
4 University of Messina, 98122 Messina, Italy.
5 Consiglio Nazionale delle Ricerche, Institute of Neuroscience, 20129 Milano, Italy.
6 Dokuz Eylul University School of Medicine, Izmir 35340, Turkey.
7 Warren Pharmaceuticals, Inc., Ossining, NY 10562, USA.


* These authors contributed equally to this study.

{dagger} To whom correspondence should be addressed. E-mail: acerami{at}kswi.org

Read the Full Text

ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)