Proton pump inhibitors (PPIs) are useful for treating gastroesophageal reflux disease (GERD), although heartburn completely resolves in only 40% of patients that take these drugs. Furthermore, long-term use of PPIs can increase risk for pneumonia, Clostridium difficile infection, and bone disorders, so other therapeutic strategies are needed. In the August issue of Gastroenterology, Boeckxstaens et al. report a new approach to reducing symptoms of GERD.
Reflux is commonly caused by transient lower esophageal sphincter relaxations (TLESRs). Agonists of the g-aminobutyric acid type B (GABAB) receptor can prevent TLESRs, so Boeckxstaens et al. tested their effects in 21 patients with persistent GERD symptoms (heartburn and regurgitation) despite PPI therapy. They found that the GABAB receptor agonist lesogaberan reduced the numbers of TLESRs in 76% of patients and reflux episodes by 47%, compared with placebo. The drug also improved lower esophageal sphincter (LES) function. The number of patients that reported adverse events was similar in the lesogaberan and placebo groups.
Although the results are Boeckxstaens et al. are encouraging, the proportion of symptom-free days after 4 weeks was only 36% in the lesogaberan group vs. 21% in the placebo group. The study participants were not typical GERD patients—63% had a history of erosive esophagitis and approximately 50% had a hiatal hernia. Further studies are therefore required to determine if lesogaberan will work in patients with other causes of GERD and what its long-term effects are.
TLESR is not the only mechanism involved in GERD—defects not targeted by GABAB agonists include hiatal hernias, obesity, impaired esophageal peristaltic function, abnormalities in compliance at the hiatus, and delayed gastric emptying. TLESR inhibitors are most likely to be useful in individuals with relatively intact gastroesophageal junction anatomy and esophageal peristaltic function. Complete elimination of GERD symptoms remains an important challenge for the GI community.
What do you think? Use the “Leave a Comment” link below to post your thoughts.
Boeckxstaens GE, Beaumont H, Mertens V, et al. Effects of lesogaberan on reflux and lower esophageal sphincter function in patients with gastroesophageal reflux disease. Gastroenterology 2010;139: 409-417.
Read the article online at Gastroenterology.
Read the accompanying FREE editorial:
Falk, GW. Inhibition of transient lower esophageal sphincter relaxation in GERD: will lesogaberan advance the field? Gastroenterology 2010;139: 377-379.