Topical Application of Nerve Growth Factor in Human Diabetic Foot Ulcers. A Study of Three Cases

Abstract

Three diabetic patients with leg or foot ulcers unresponsive to conventional therapies were treated with topical application of Nerve Growth Factor (NGF). The results showed that NGF promotes healing after 5 - 14 weeks of treatment. This study suggests that the use of topical application of NGF may represent a new useful tool for the management of difficult diabetic ulcers.

Key words

Nerve growth factor - diabetes - cutaneous ulcer - neuropathy

References

• 1 Adler A I, Boyko E J, Ahroni J H, Smith D G. Lower-extremity amputation in diabetes. The independent effects of peripheral vascular disease, sensory neuropathy, and foot ulcers.  Diabetes Care. 1999;  22 1029-1035
• 2 Anand P, Terenghi G, Warner G, Kopelman P, Williams-Chestnut R E, Sinicropi D V. The role of endogenous nerve growth factor in human diabetic neuropathy.  Nat Med. 1996;  2 703-707
• 3 Bernabei R, Landi F, Bonini S, Onder G, Lambiase A, Pola R, Aloe L. Effect of topical application of nerve-growth factor on pressure ulcers.  Lancet. 1999;  354 307
• 4 Bocchini V, Angeletti P U. The nerve growth factor: purification as a 30 000-molecular-weight protein.  Proc Natl Acad Sci USA. 1969;  64 787-794
• 5 Di Marco E, Marchisio P C, Bondanza S, Franzi A T, Cancedda R, De Luca M. Growth-regulated synthesis and secretion of biologically active nerve growth factor by human keratinocytes.  J Biol Chem. 1991;  266 21718-21722
• 6 Lambiase A, Rama P, Bonini S, Caprioglio G, Aloe L. Topical treatment with nerve growth factor for corneal neurotrophic ulcers.  N Engl J Med. 1998;  338 1174-1180
• 13 Landi F, Aloe L, Russo A, Cesari M, Onder G, Bonini S, Carbonin P U, Bernabei R. Topical treatment of pressure ulcers with nerve growth factor: a randomized clinical trial.  Ann Intern Med. 2003;  139 635-641
• 7 Levi-Montalcini R. The nerve growth factor 35 years later.  Science. 1987;  237 1154-1162
• 8 Matsuda H, Koyama H, Sato H, Sawada J, Itakura A, Tanaka A, Matsumoto M, Konno K, Ushio H, Matsuda K. Role of nerve growth factor in cutaneous wound healing: accelerating effects in normal and healing-impaired diabetic mice.  J Exp Med. 1998;  187 297-306
• 9 Turrini P, Gaetano C, Antonelli A, Capogrossi M C, Aloe L. Nerve growth factor induces angiogenic activity in a mouse model of hindlimb ischemia.  Neurosci Lett. 2002;  323 109-112
• 10 Tuveri M A, Generini S, Matucci-Cerinic M, Aloe L. NGF, a useful tool in the treatment of chronic vasculitic ulcers in rheumatoid arthritis.  Lancet. 2000;  356 1739-1740
• 11 Wagner Jr F W. The dysvascular foot: a system for diagnosis and treatment.  Foot Ankle. 1981;  2 64-122
• 12 Wilkinson D I, Theeuwes M J, Farber E M. Nerve growth factor increases the mitogenicity of certain growth factors for cultured human keratinocytes: a comparison with epidermal growth factor.  Exp Dermatol. 1994;  3 239-245