1. Academic Validation
  2. Oral retinoic acid metabolism blocking agent Rambazole for plaque psoriasis: an immunohistochemical study

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

  • Br J Dermatol. 2007 Feb;156(2):263-70. doi: 10.1111/j.1365-2133.2006.07660.x.
H J Bovenschen 1 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
Affiliations

Affiliation

  • 1 Department of Dermatology, Radboud University Nijmegen Medical Center, NL- 6500 HB Nijmegen, The Netherlands. j.bovenschen@derma.umcn.nl
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.

Figures
Products