The American Journal of Surgery
Volume 193, Issue 1 , Pages 49-54 , January 2007

Talactoferrin alfa, a recombinant human lactoferrin promotes healing of diabetic neuropathic ulcers: a phase 1/2 clinical study

  • Thomas E. Lyons, D.P.M.

      Affiliations

    • Beth Israel Deaconess Medical Center and Harvard Medical School, Palmer 321 A, West Campus, Boston, MA 02215, USA
    • ,
  • Michael S. Miller, D.O.

      Affiliations

    • The Wound Healing Center, Terre Haute, IN, USA
    • ,
  • Thomas Serena, M.D.

      Affiliations

    • Penn North Centers for Advanced Wound Care, Warren, PA, USA
    • ,
  • Peter Sheehan, M.D.

      Affiliations

    • New York University School of Medicine Hospital for Joint Diseases, New York, NY, USA
    • ,
  • Lawrence Lavery, D.P.M.

      Affiliations

    • Scott and White Hospital, Temple, TX, USA
    • ,
  • Robert S. Kirsner, M.D., Ph.D.

      Affiliations

    • University of Miami School of Medicine, Miami, FL, USA
    • ,
  • David G. Armstrong, D.P.M., Ph.D.

      Affiliations

    • Scholl’s Center for Lower Extremity Ambulatory Research at Rosalind Franklin University of Medicine and Science, Chicago, IL, USA
    • ,
  • Amber Reese, B.A.

      Affiliations

    • Agennix Inc, Houston, TX, USA
    • ,
  • Ernest W. Yankee, Ph.D.

      Affiliations

    • Agennix Inc, Houston, TX, USA
    • ,
  • Aristidis Veves, M.D., D.Sc.

      Affiliations

    • Beth Israel Deaconess Medical Center and Harvard Medical School, Palmer 321 A, West Campus, Boston, MA 02215, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1-617-632-7075; fax: +1-617-632-7090.

Received 28 March 2006 ,Revised 23 July 2006

References 

  1. Ramsey SD, Newton K, Blough D, et al. Incidence, outcomes, and cost of foot ulcers in patients with diabetes. Diabetes Care. 1999;22:382–387
  2. Consensus Development Conference on Diabetic Foot Wound Care. American Diabetes Association. Diabetes Care. 1999;22:1354–1360
  3. Veves A, Falanga V, Armstrong DG, Sabolinski ML. The Apligraf Diabetic Foot Ulcer Study (Graftskin, a human skin equivalent, is effective in the management of noninfected neuropathic diabetic foot ulcers: a prospective randomized multicenter clinical trial). Diabetes Care. 2001;24:290–295
  4. Wieman TJ, Smiell JM, Su Y. Efficacy and safety of a topical gel formulation of recombinant human platelet-derived growth factor-BB (becaplermin) in patients with chronic neuropathic diabetic ulcers (A phase III randomized placebo-controlled double-blind study). Diabetes Care. 1998;21:822–827
  5. Ward PP, Pidington CS, Cunningham G, et al. A system for production of commercial quantities of human lactoferrin: a broad spectrum natural antibiotic. Biotechnology (N Y). 1995;13:498–503
  6. Miehlke S, Reddy R, Osato MS, et al. Direct activity of recombinant human lactoferrin against Helicobacter pylori. J Clin Microbiol. 1996;34:2593–2594
  7. Cumberbatch M, Dearman RJ, Uribe-Luna S, et al. Regulation of epidermal Langerhans cell migration by lactoferrin. Immunology. 2000;100:21–28
  8. Biet F, Locht C, Kremer L. Immunoregulatory functions of interleukin 18 and its role in defense against bacterial pathogens. J Mol Med. 2002;80:147–162
  9. Kampfer H, Kalina U, Muhl H, et al. Counterregulation of interleukin-18 mRNA and protein expression during cutaneous wound repair in mice. J Invest Dermatol. 1999;113:369–374
  10. Mann A, Breuhahn K, Schirmacher P, Blessing M. Keratinocyte-derived granulocyte-macrophage colony stimulating factor accelerates wound healing: stimulation of keratinocyte proliferation, granulation tissue formation, and vascularization. J Invest Dermatol. 2001;117:1382–1390
  11. Kurose I, Yamada T, Wolf R, Granger DN. P-selectin-dependent leukocyte recruitment and intestinal mucosal injury induce by lactoferrin. J Leukoc Biol. 1994;55:771–777
  12. Loots MA, Lamme EN, Zeegelaar J, et al. Differences in cellular infiltrate and extracellular matrix of chronic diabetic and venous ulcers versus acute wounds. J Invest Dermatol. 1998;111:850–857
  13. Falanga V. Wound healing and its impairment in the diabetic foot. Lancet. 2005;366:1736–1743
  14. Hayes TG, Falchook GF, Varadhachary GR, et al. Phase I trial of oral talactoferrin alfa in refractory solid tumors. Invest New Drugs 2005;Sep 20 [Epub ahead of print].
  15. Tsuda H, Sekine K, Fujita K, Ligo M. Cancer prevention by bovine lactoferrin and underlying mechanisms—a review of experimental and clinical studies. Biochem Cell Biol. 2002;80:131–136
  16. Marston WA, Hanft J, Norwood P Dermagraft Diabetic Foot Ulcer Study Group. The efficacy and safety of Dermagraft in improving the healing of chronic diabetic foot ulcers: results of a prospective randomized trial. Diabetes Care. 2003;26:1701–1705
  17. Veves A, Sheehan P, Pham TH. A comparison of a new topical treatment, Promogranversus standard treatment in the management of diabetic foot ulcers. Arch Surg. 2002;137:822–827
  18. Margolis DJ, Kantor J, Berlin JA. Healing of diabetic neuropathic foot ulcers receiving standard treatment: a meta-analysis. Diabetes Care. 1999;22:692–695

 Supported in part by Agennix, Inc. and the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institute of Health.David J. Margollis, M.D., Ph.D., served as the external NIH-approved Safety Officer.

PII: S0002-9610(06)00651-9

doi: 10.1016/j.amjsurg.2006.07.010

The American Journal of Surgery
Volume 193, Issue 1 , Pages 49-54 , January 2007

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