Bringing GERD Management up to PAR-2

Proton pump inhibitors (PPIs) are extremely effective for mucosal healing of reflux esophagitis, but less so for relieving the symptom of heartburn. PPIs block the secretion of gastric acid, the caustic effects of which have been assumed to be the primary culprit in the pathogenesis of reflux esophagitis. However, mounting data suggest that reflux-stimulated, immune-mediated mechanisms may underlie the development of esophagitis in patients with gastroesophageal reflux disease (GERD). Thus, the future of GERD therapy, particularly for patients who are refractory to PPIs, may be the targeting of proteins such as proteinase-activated receptor-2, which have central roles in the generation of immune-mediated esophageal mucosal damage and in eliciting the symptom of heartburn.