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The Vitamin D Analog Calcipotriol Combined with Aminolevulinate‐Mediated Photodynamic Therapy for Human Psoriasis: A Proof‐of‐Principle Study
Author(s) -
Maytin Edward V.,
Honari Golara,
Khachemoune Amor,
Taylor Charles R.,
Ortel Bernhard,
Pogue Brian W.,
SznycerTaub Nathaniel,
Hasan Tayyaba
Publication year - 2012
Publication title -
israel journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.908
H-Index - 54
eISSN - 1869-5868
pISSN - 0021-2148
DOI - 10.1002/ijch.201200005
Subject(s) - calcipotriol , psoriasis , photodynamic therapy , protoporphyrin ix , cancer research , chemistry , calcitriol , vitamin d and neurology , retinoic acid , methotrexate , vitamin , pharmacology , dermatology , medicine , immunology , biochemistry , organic chemistry , gene
Abstract We previously showed that select agents (methotrexate or vitamin D), when administered as a preconditioning regimen, are capable of promoting cellular differentiation of epithelial cancer cells while simultaneously enhancing the efficacy of 5‐aminolevulinic acid (ALA)‐mediated photodynamic therapy (PDT). In solid tumors, pretreatment with vitamin D simultaneously promotes cellular differentiation and leads to selective accumulation of target porphyrins (mainly protoporphyrin IX, PpIX) within diseased tissue. However, questions of whether or not the effects upon cellular differentiation are inexorably linked to PpIX accumulation, and whether these effects might occur in hyperproliferative noncancerous tissues, have remained unanswered. In this paper, we reasoned that psoriasis, a human skin disease in which abnormal cellular proliferation and differentiation play a major role, could serve as a useful model to test the effects of prodifferentiating agents upon PpIX levels in a nonneoplastic setting. In particular, vitamin D, a treatment for psoriasis that restores (i.e., increases) differentiation, might increase PpIX levels in psoriatic lesions and facilitate their responsiveness to ALA‐PDT. This concept was tested in a pilot study of seven patients with bilaterally matched psoriatic plaques. A regimen in which calcipotriol 0.005 % ointment was applied for six days prior to ALA‐PDT using blue light led to preferential increases in PpIX (ca. 50 %), and reductions in thickness, redness, scaling, and itching in the pretreated plaques. The results suggest that a larger clinical trial is warranted to confirm a role for combination treatments with vitamin D and ALA‐PDT for psoriasis.