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实验医学模型在评估肥胖和暴食障碍新型治疗方法的疗效、副作用和作用机制方面的应用。

Utility of an experimental medicine model to evaluate efficacy, side-effects and mechanism of action of novel treatments for obesity and binge-eating disorder.

机构信息

School of Psychology, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom.

P1vital Ltd, Howbery Park, Wallingford, OX10 8BA, United Kingdom; P1vital Products Ltd, Howbery Park, Wallingford, OX10 8BA, United Kingdom.

出版信息

Appetite. 2022 Sep 1;176:106087. doi: 10.1016/j.appet.2022.106087. Epub 2022 May 16.

Abstract

Obesity and Binge-Eating Disorder (BED) are prevalent conditions that are associated with increased risk of morbidity and mortality. There is evidence that the use of pharmacotherapy alongside behavioural treatments can improve quality of life and reduce disease risk for patients with these disorders. However, there are few approved drug therapies for obesity, and these are limited by poor efficacy and/or side effects and only one drug has been approved for the treatment of BED. There is considerable potential to use experimental medicine models to identify new drug treatments for obesity and BED, with greater efficacy and an improved side effect profile, at an early stage of development. Here, we present a model developed in our laboratory that incorporates both behavioural and neuroimaging measures which can be used to facilitate drug development for obesity and BED. The results from validation studies conducted to date using our model suggest that it is sensitive to the effects of agents with behavioural, neurophysiological and neuropharmacological mechanisms of action known to be associated with weight loss and reductions in binge eating. Future studies using the model will be valuable to evaluate the potential efficacy and side-effects of new candidate drugs at an early stage in the development pipeline for both obesity and BED.

摘要

肥胖症和暴食症(BED)是常见的疾病,它们与发病率和死亡率的增加有关。有证据表明,在行为治疗的基础上联合使用药物治疗,可以提高生活质量并降低这些疾病患者的疾病风险。然而,目前仅有少数几种肥胖症的药物治疗方法得到批准,这些方法的疗效较差,且存在副作用,并且仅有一种药物被批准用于治疗 BED。在开发的早期阶段,利用实验医学模型来识别新的肥胖症和 BED 药物治疗方法,这些方法具有更好的疗效和改善的副作用特征,具有很大的潜力。在这里,我们介绍了我们实验室开发的一种模型,该模型结合了行为和神经影像学测量方法,可用于促进肥胖症和 BED 的药物开发。迄今为止,使用我们的模型进行的验证研究的结果表明,该模型对具有行为、神经生理和神经药理学作用机制的药物的作用敏感,这些机制与体重减轻和暴食减少有关。未来使用该模型的研究将有助于评估新候选药物在肥胖症和 BED 药物开发管道的早期阶段的潜在疗效和副作用。

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