Results from a Phase I Clinical Trial of HBED

  • Robert W. Grady
  • Margaret W. Hilgartner
  • Patricia J. Giardina
  • Arline D. Salbe
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 356)


The experience of the past dozen years clearly indicates that iron plays a significant role in the pathogenesis of a wide variety of disease states apart from hemochromatosis. 1 In cases of rheumatoid arthritis and reperfusion injury, iron catalyzes the formation of free radicals which destroy membranes and thereby lead to tissue damage. Sequestration of this iron would obviate much of this damage. In lymphopro-liferative disorders and parasitic diseases such as malaria, iron serves as an essential nutrient for dividing cells. Withholding iron would inhibit cell division and hence slow the progression of such diseases. While unlikely to affect cures, chelation of iron would undoubtedly be of benefit as adjunctive therapy in these and related disorders.


Serum Ferritin Iron Overload Iron Chelator Serum Ferritin Level Chelation Therapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    C. Hershko, Iron chelators in medicine, Molec. Aspects Med. 13: 113 (1992).CrossRefGoogle Scholar
  2. 2.
    P.J. Giardina, R.W. Grady, K.H. Ehlers, S. Burstein, J.H. Graziano, A.L. Markenson and M.W. Hilgartner, Current therapy of Cooley’s anemia: a decade of experience with subcutaneous desferrioxamine, Ann. N. Y. A. S. 612: 275 (1990).CrossRefGoogle Scholar
  3. 3.
    R.W. Grady, and C. Hershko, HBED: a potential oral iron chelator, Ann. N. Y. A. S. 612: 361 (1990).CrossRefGoogle Scholar
  4. 4.
    G.M. Brittenham, Pyridoxal isonicotinoyl hydrazone, effective iron chelation after oral administration, Ann. N. Y. A. S. 612: 315 (1990).CrossRefGoogle Scholar
  5. 5.
    R.C. Hider, S. Singh, J.B. Porter, and E.R. Huehns, The development of hydroxypyridin-4-ones as orally active iron chelators, Ann. N. Y. A. S. 612: 327 (1990).CrossRefGoogle Scholar
  6. 6.
    R.J. Bergeron, J. Wiegand, J.B. Dionis, M. Egli-Karmakka, J. Frei, A. Huxley-Tencer, and H.H. Peter, Evaluation of desferrithiocin and its synthetic analogues as orally effective iron chelators, J. Med. Chem. 34: 2072 (1991).PubMedCrossRefGoogle Scholar
  7. 7.
    B.E. Hedlund, P.E. Hallaway, and J.R. Mahoney, High molecular weight forms of deferoxamine: novel therapeutic agents for treatment of iron-mediated tissue injury, Adv. Exp. Med. Biol. 264: 229 (1990).PubMedCrossRefGoogle Scholar
  8. 8.
    R.J. Bergeron, J. Wiegand, J.S. McManis, and P.T. Perumal, Synthesis and biological evaluation of hydroxamate-based iron chelators, J. Med. Chem. 34: 3182 (1991).PubMedCrossRefGoogle Scholar
  9. 9.
    N.F. Olivieri, D.M. Templeton, G. Koren, D. Chung, M.H. Freedman, and R.A. McClelland, Evaluation of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in iron-loaded patients, Ann. N. Y. A. S. 612: 369 (1990).CrossRefGoogle Scholar
  10. 10.
    P. Tondury, G.J. Kontoghiorghes, A. Ridolfi-Luthy, A. Hirt, A.V. Hoffbrand, A.M. Lottenbach, T. Sonderegger, and H.P. Wagner, L1 (1,2-dimethyl-3-hydroxypyrid-4-one) for oral iron chelation in patients with ß-thalassemia, Br. J. Haematol. 76: 550 (1990).PubMedCrossRefGoogle Scholar
  11. 11.
    M.B. Agarwal, S.S. Gupte, D. Vasandani, C. Viswanathan, R.R. Puniyani, J. Rananathan, D.E. Massil, S. Shah, G.C. Rajyadhyaksha, and A.A. Bhave, Efficacy and safety of 1,2-dimethyl-3-hydroxypyrid-4-one (L1) as an oral iron chelator in patients of ß-thalassemia major with iron overload, J. Assoc. Phys. (India) J. A. P. I. 39: 669 (1991).Google Scholar
  12. 12.
    F.N. Al-Refaie, B. Wonke, A.V. Hoffbrand, D.G. Wickens, P. Nortey, and G.J. Kontoghiorghes, Efficacy and possible adverse effects of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in thalassemia major, Blood, 80: 593 (1992).PubMedGoogle Scholar
  13. 13.
    V. Berdoukas, P. Bentley, H. Frost and H.P. Schnebli, Tocicity of oral iron chelator L1, The Lancet, 341: 1088 (1993).CrossRefGoogle Scholar
  14. 14.
    C. Hershko, Development of oral iron chelator L1, The Lancet, 341: 1088 (1993).CrossRefGoogle Scholar
  15. 15.
    G.J. Kontoghiorghes, M.B. Agarwal, P. Tondury, M.J. Kersten, M. Jaeger, G. Vreugdenhil, A. Vania and Y.E. Rahman, Future of oral iron chelator deferiprone (L1), The Lancet, 341: 1479 (1993).CrossRefGoogle Scholar
  16. 16.
    R.W. Grady, and A. Jacobs, The screening of potential iron chelating drugs, in: “Development of Iron Chelators for Clinical Use: Proceedings of the Second Symposium on the Development of Iron Chelators for Clinical Use,” A.E. Martell, W.F. Anderson and D.G. Badman, eds., Elsevier North Holland, Inc., New York (1981).Google Scholar
  17. 17.
    R.W. Grady, A.D. Salbe, M.W. Hilgartner and P.J. Giardina, Preliminary results from a phase I clinical trial of HBED, in: “The Development of Iron Chelators for Clinical Use,” R.J. Bergeron and G.M. Brittenham, eds., CRC Press, Inc., Boca Raton (1993).Google Scholar
  18. 18.
    C.M. Peterson, J.H. Graziano, R.W. Grady, R.L. Jones, H.V. Vlassara, V.C. Canale, D.R. Miller and A. Cerami, Chelation studies with 2,3-dihydroxybenzoic acid in patients with ß-thalassaemia major, Br. J. Haematol., 33: 477 (1976).PubMedCrossRefGoogle Scholar
  19. 19.
    M.J. Pippard, S.T. Callender, and C.A. Finch, Ferrioxamine excretion in iron loaded man, Blood 60: 288 (1982).PubMedGoogle Scholar
  20. 20.
    J.A. Harris, and F.G. Benedict, A biometric study of basal metabolism in man, in: “Publication No. 279,” Carnegie Institution, Washington, D. C. (1919).Google Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Robert W. Grady
    • 1
  • Margaret W. Hilgartner
    • 1
  • Patricia J. Giardina
    • 1
  • Arline D. Salbe
    • 2
  1. 1.Department of PediatricsCornell University Medical CollegeNew YorkUSA
  2. 2.Department of MedicineCornell University Medical CollegeNew YorkUSA

Personalised recommendations