Blood Journal
Leading the way in experimental and clinical research in hematology

Effect of the anti-hepcidin Spiegelmer® lexaptepid on inflammation-induced decrease in serum iron in humans

  1. Lucas T. van Eijk1,
  2. Aaron S.E. John2,
  3. Frank Schwoebel3,
  4. Luciana Summo3,
  5. Stéphanie Vauléon3,
  6. Stefan Zöllner3,
  7. Coby M. Laarakkers4,
  8. Matthijs Kox5,
  9. Johannes G. van der Hoeven1,
  10. Dorine W. Swinkels4,
  11. Kai Riecke3, and
  12. Peter Pickkers1,*
  1. 1 Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, Netherlands;
  2. 2 Radboud Institute for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands;
  3. 3 NOXXON Pharma AG, Berlin, Germany;
  4. 4 Department of Laboratory Medicine, Laboratory of Genetic, Endocrine and Metabolic Diseases, Radboud University Medical Center, Nijmegen, Netherlands;
  5. 5 Department of Anesthesiology, Radboud University Medical Center, Nijmegen, Netherlands
  1. * Corresponding author; email: peter.pickkers{at}radboudumc.nl

Key points

  • Lexaptepid modulates the inflammation-induced decrease in serum iron during experimental human endotoxemia.

  • Hepcidin targeting with the novel compound lexaptepid may be a viable approach to the treatment of anemia of inflammation in humans,

Abstract

Increased hepcidin production is key to the development of anemia of inflammation. We investigated whether lexaptepid, an anti-hepcidin L-oligoribonucleotide, prevents the decrease in serum iron during experimental human endotoxemia. This randomized, double-blind, placebo-controlled trial was carried out in 24 healthy males. At T=0 hours, 2 ng/kg Escherichia coli lipopolysaccharide was intravenously administered, followed by an intravenous injection of 1.2 mg/kg lexaptepid or placebo at T=0.5 hours. The lipopolysaccharide-induced inflammatory response was similar in subjects treated with lexaptepid or placebo regarding flu-like symptoms, body temperature, C-reactive protein, leucocyte counts and cytokine concentrations. At T=9 hours, serum iron had increased by 15.9±9.8 µmol/L from baseline in lexaptepid-treated subjects compared with a decrease of 8.3±9.0 µmol/L in controls (P<0.0001). This study delivers proof of concept that lexaptepid achieves clinically relevant hepcidin inhibition enabling investigations in the treatment of anemia of inflammation. This trial was registered at www.clinicaltrial.gov #NCT01522794.

  • Submitted March 28, 2014.
  • Accepted July 23, 2014.