Ilan Yaron
Department of Medicine, Hadassah Medical Center, Faculty of Medicine, Hebrew University, Jerusalem POB12000, Israel.
J Pers Med. 2022 Aug 10;12(8):1303. doi: 10.3390/jpm12081303.
Chronic diseases are a significant healthcare problem. Partial or complete non-responsiveness to chronic therapies is a significant obstacle to maintaining the long-term effect of drugs in these patients. A high degree of intra- and inter-patient variability defines pharmacodynamics, drug metabolism, and medication response. This variability is associated with partial or complete loss of drug effectiveness. Regular drug dosing schedules do not comply with physiological variability and contribute to resistance to chronic therapies. In this review, we describe a three-phase platform for overcoming drug resistance: introducing irregularity for improving drug response; establishing a deep learning, closed-loop algorithm for generating a personalized pattern of irregularity for overcoming drug resistance; and upscaling the algorithm by implementing quantified personal variability patterns along with other individualized genetic and proteomic-based ways. The closed-loop, dynamic, subject-tailored variability-based machinery can improve the efficacy of existing therapies in patients with chronic diseases.
慢性病是一个重大的医疗保健问题。对慢性治疗的部分或完全无反应是维持这些患者药物长期疗效的重大障碍。患者内和患者间的高度变异性决定了药效学、药物代谢和药物反应。这种变异性与药物有效性的部分或完全丧失有关。常规的给药方案不符合生理变异性,并且导致对慢性治疗产生耐药性。在本综述中,我们描述了一个克服耐药性的三相平台:引入不规则性以改善药物反应;建立深度学习闭环算法以生成个性化的不规则模式来克服耐药性;以及通过实施量化的个体变异性模式以及其他基于个体基因和蛋白质组学的方法来扩大算法规模。基于闭环、动态、个体定制的变异性机制可以提高现有疗法对慢性病患者的疗效。