Dermatitis Research Today is a free monthly online journal that collates and summarizes the latest research about Dermatitis, including details on contact-, seborrheic-, atopic-, allergic-dermatitis, treatment.

Blockade of experimental atopic dermatitis via topical NF-kappaB decoy oligonucleotide.

Dajee M, Muchamuel T, Schryver B, Oo A, Alleman-Sposeto J, De Vry CG, Prasad S, Ruhrmund D, Shyamsundar R, Mutnick D, Mai K, Le T, Parham C, Zhang J, Komuves L, Colby T, Hudak S, McEvoy LM, Ehrhardt RO

Department of Research, Corgentech. Inc., South San Francisco, California, USA.

Atopic dermatitis (AD) is a common chronic skin inflammatory disease. Long-term use of topical corticosteroids in skin inflammation poses risks of systemic and local side effects. The NF-kappaB transcription factor family plays a central role in the progression and maintenance of AD. This study explores the possibility of using topical NF-kappaB Decoy as a novel therapeutic alternative for targeting Th1/Th2-driven skin inflammation in experimental AD. A high-affinity, topical NF-kappaB Decoy developed for human efficacy demonstrates: (i) efficient NF-kappaB Decoy penetration in pig skin, (ii) NF-kappaB Decoy nuclear localization in keratinocytes and key immune cells, and (iii) potent "steroid-like" efficacy in a chronic dust-mite antigen skin inflammation treatment model. NF-kappaB Decoy exerts its anti-inflammatory action through the effective inhibition of essential regulators of inflammation and by induction of apoptosis of key immune cells. Unlike betamethasone valerate (BMV), long-term NF-kappaB Decoy treatment does not induce skin atrophy. Moreover, topical NF-kappaB Decoy, in contrast to BMV, restores compromised stratum corneum integrity and barrier function. Steroid withdrawal causes rapid rebound of inflammation, while the NF-kappaB Decoy therapeutic benefit was maintained for weeks. Thus, topical NF-kappaB Decoy provides a novel mechanism of reducing chronic skin inflammation with improved skin homeostasis and minimal side effects.

Published 17 July 2006 in J Invest Dermatol, 126(8): 1792-803.
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