1085 Mechanism of oral and topical polyprenol action in atopic dermatitis

Wednesday, 14 October 2015
Hall D1 Foyer (Floor 3) (Coex Convention Center)

Galina Kuznecova , Allergy and Dermatology, Preventive Medicine Institute, Riga, Latvia

Ivans Sergejs Kuznecovs, MD , Allergy and Immunology, Preventive Medicine Institute, Riga, Latvia

Background: Atopic dermatitis (AD) presence and activity correlates with loss of filaggrin. Dysregulation of DPAGT1 (Dolichyl-phosphate (UDP-N-acetylglucosamine) N-acetylglucosaminephosphotransferase 1 (GlcNAc-1-P transferase) causes disturbances in filaggrin expression.  The findings indicate that DPAGT1 overexpression in keratinocytes treated with IL-4 and IL-13 can be overcomed by PP, which provides a dolichyl phosphate substitute for DPAGT1 normal expression, N-glycosylation and filaggrin loss prevention. The aim of the present study is to investigate the clinical efficacy of Polyprenol (PP) in children with AD.
Methods: SCORAD index was used to measure the severity of the disease and to evaluate the effect of treatment in 100 children (6-24 months old). Leukotriene E4 and dolichol (Dol) were assayed in urinal excretion, immunoCAP total IgE levels were measured in serum, dolichol phosphate N-acetyl-glucosamine-1 phosphate transferase (GPT) activity was defined in dermal fibroblasts by metaboling labeling (ML) method with [2-(3)H]-mannose.  PP (1 mg/kg/day, per os) and topical ointment with PP 5% were given in a randomized, double-blind, placebo-controlled study. The effect of the treatment was evaluated weekly up to six months.

Results: Initially patients with AD were found to have a statistically significant increase in leukotriene E4 (4-fold) and Dol (6,2-fold) excretion, total Ig E level and GPT activity in fibroblasts in comparison to controls. Overexpression of DPAGT1 was 5-fold higher in AD skin biopsies than in normal skin biopsies. AD cells differ from normal one in filaggrin content lost by 3-4 times. IL-4 and IL-13 cause overexpression and abberant N-glycosylation of filaggrin in DPC. The study showed overexpression of DPAGT1 and 6-fold DPC intermediates decrease in keratinocytes in presence of IL-13 and 2-fold in presence of IL-4 cells.The normalization up to 90% of Dol excretion was achieved after 2 weeks of treatment, IgE and E4 in 3 weeks, GPT after one month in 70% of patients with remission for more than 6 month. Significant difference in AD scores between  PP and placebo (P <0.01) was recognized.

Conclusion: The present study demonstrates alleviation of AD in children with the use of oral and topical Polyprenol  . The mechanism of activity  involves the main links of AD pathogenesis.