Oral retinoic acid metabolism blocking agent Rambazole for plaque psoriasis: an immunohistochemical study.

Abstract

BACKGROUND:

The novel systemic all-trans retinoic acid metabolism blocking agent (RAMBA) R115866 (Rambazole(TM); Barrier Therapeutics, Geel, Belgium; further referred to as rambazole) increases intracellular levels of endogenous all-trans retinoic acid (RA). Well-known effects of RA are normalization of aberrant epithelial growth and differentiation. Hence, rambazole might be beneficial in the treatment of plaque psoriasis.

OBJECTIVES:

The dynamics of epidermal proliferation, keratinization, lesional T-cell subsets and cells expressing natural killer (NK)-receptors in plaque psoriasis were assessed during treatment with rambazole, as part of a phase IIa open-label clinical trial.

METHODS:

Six patients were treated with rambazole, 1 mg, once daily, for 8 weeks. At weeks 0, 2 and 8, psoriatic plaque severity scores (SUM) and biopsies from a target lesion were assessed. Epidermal proliferation (Ki67), keratinization markers (K10, K13, K19), T-cell subsets (CD3, CD4+, CD8+, CD45RO+, CD45RA+, CD2+, CD25+, GITR+) and cells expressing NK-receptors (CD94, CD161) were immunohistochemically stained and quantified with image analysis.

RESULTS:

At week 2 the mean SUM-score was virtually equal to baseline, which was accompanied immunohistochemically by equal epidermal hyperproliferation, a nonsignificant decrease in K10 positive epidermis and, overall, a nonsignificant increase in immunocyte subsets. At week 8, in contrast, plaque severity was reduced by 34% from baseline (P < 0.05). Improvements were also detected for epidermal proliferation (-63%; P < 0.01) and K10 expression (+29%; P < 0.01), compared with baseline. No induction of retinoid-specific keratinization (K13, K19) was observed. A nonsignificant reduction of all pathogenic T-cell subsets and cells expressing NK-receptors was observed at week 8 of treatment (P > 0.05).

CONCLUSIONS:

Clinical efficacy of rambazole is primarily the result of restoring proliferation (Ki67) and differentiation (K10) of epidermal keratinocytes. Secondly, relevant T-cell subsets and cells expressing NK-receptors showed nonsignificant reductions after 8 weeks of treatment with rambazole.

• Authors: H J Bovenschen, M E Otero, A M G Langewouters, I M J J van Vlijmen-Willems, D W A van Rens, M M B Seyger, P C M van de Kerkhof
• Journal: The British journal of dermatology (Br J Dermatol) Vol. 156 Issue 2 Pg. 263-70 (Feb 2007) ISSN: 0007-0963 [Print] England
• PMID: 17223865 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzothiazoles
• Dermatologic Agents
• Keratolytic Agents
• Triazoles
• Tretinoin
• R 115866

Topics

• Administration, Oral
• Adult
• Benzothiazoles (administration & dosage)
• Cell Proliferation (drug effects)
• Dermatologic Agents (administration & dosage)
• Female
• Humans
• Immunohistochemistry (methods)
• Keratolytic Agents (antagonists & inhibitors)
• Male
• Middle Aged
• Psoriasis (drug therapy)
• Tretinoin (antagonists & inhibitors)
• Triazoles (administration & dosage)