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However, preclinical studies demonstrate therapeutic effects with once-daily or even less frequent administration, suggesting tissue distribution, receptor binding, or cellular signaling effects extend beyond plasma clearance

Second, common in vitro surrogates such as TR146 cell model are useful for studying mechanism but do not reproduce the stratified buccal epithelium

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The dramatic clinical effect of COL5A1 haploinsufficiency is surprising, given that collagen V is a quite minor constituent of collagen in skin, tendon, and ligament, but the clinical phenotype clearly supports an important function for collagen V in the maintenance of biomechanical integrity of collagenous matrix