Editorial: ONO‐2952 in irritable bowel syndrome with diarrhoea – authors’ reply

Abstract

2. Mitsui K. Effects of ono-2925, a novel translocator protein 18 kDa antagonist, on stress-induced rectal hyperalgesia and defecation in rats. We thank Drs Nee and Lembo 1 for their editorial commenting on our article. 2 We would like to respond by pointing out the need for a treatment for irritable bowel syndrome with diarrhoea (IBS-D) that addresses the increased frequency of loose, watery stools and the increased pain caused by stress. Stress-induced diarrhoea and pain are regarded as key factors in IBS, although they are not much discussed. They are targets for the treatment of IBS with behavioural approaches that focus on the use of paced respiration and relaxation training to regulate stress, and a recent review of these techniques was published in the stress chapter of the Rome IV project.3 Unfortunately, these behavioural techniques are time-consuming, and are not widely available. A new drug such as ONO-2952, 1 if confirmed in subsequent studies, would make it possible for this aspect of IBS to be addressed by primary care practitioners. We look forward to follow-up studies which would make it possible to select patients who are uniquely responsive to this category of drug. In animal studies, rats were selected who were selectively trained to avoid fear-producing shocks, and these subjects were uniquely responsive to the drug; however, in the human study reported to date, no such selection of subjects was done to minimise recruitment problems. New studies could include patients who are selected for their responsiveness to the effects of anxiety.Future studies should also test higher doses of ONO-2952 to identify whether the drug is uniquely associated with actions in the brain or has peripheral effects as well. To date, there is no reason to expect the highest dose of the study drug to be 60 mg/day, but more data are needed on higher doses. Thus, there is considerable room for future research to expand on this unique preliminary study. ACKNOWLEDGEMENT

Mitochondrial translocator protein deficiency exacerbates pathology in acute experimental ulcerative colitis

“…In preclinical rat models, ONO-2952 attenuated stress-induced defecation and rectal hyperalgesia (Kawahara et al, 2018). In the Phase 2 trial, ONO-2952 showed evidence for clinical efficacy with promising trends supporting its consideration as a potential treatment (Whitehead et al, 2017). Similarly, flunitrazepam, albeit a non-selective TSPO-binding drug, could protect the intestinal mucosa against DSS-induced damage (Ostuni et al, 2010).…”