Translational gastrointestinal pharmacology in the 21st century: 'the lesogaberan story'

The development of the novel gamma-aminobutyric acid type-B receptor (GABA(B)) agonist lesogaberan is presented as an example of a partly successful translational strategy in the field of gastroenterology. Data on transient lower esophageal sphincter relaxations (TLESRs) and gastroesophageal reflux inhibition from preclinical models translated well to clinical studies in healthy volunteers and patients with gastroesophageal reflux disease (GERD). Animal models have also been used successfully to predict the effect of other target mechanisms on TLESRs in humans. However, while translation of physiology to symptomatology in patients with GERD was achieved, the effect size was too small to be of clinical significance. A deeper understanding of the cause of symptoms in different patient categories is therefore required.