Pediatric Pharmacogenomics and Personalized Medicine

描述(由申请人提供)：临床医生、制药公司和监管机构面临的一个主要挑战是更好地了解个体发育和遗传变异对从早产儿和足月新生儿到婴儿、儿童和青少年的整个儿科年龄范围内药物处置和反应的可变性的相对贡献。在过去的25年里，关于遗传变异对成人药物处置和反应的可变性的贡献的知识有了很大的增加，但药物遗传学和药物基因组学原理在儿科药物治疗中的应用却远远落后。将药物基因组学和个性化药物的成人经验外推到不同年龄和发育阶段的儿科患者充满了许多挑战。一些儿科疾病与成人没有相关性，或者与成人相比在儿童中更常见。同样，一些药物不良反应是儿童独有的，或者在儿童中发生的频率更高。与成人相比，儿科药物遗传学和药物基因组学涉及额外的复杂性测量，因为发育过程或个体发育的变异性叠加在遗传变异上。在药物处置和反应的背景下，个体发育所带来的额外复杂性表现为与基于成人经验的预期相比，在剂量要求、药物疗效或毒性风险方面的意外差异。这项提议的主要目标是在密苏里州堪萨斯城的儿童慈悲医院和诊所，由个性化医学和治疗创新中心以及临床药理学和医疗治疗部组织正在举行的关于“儿科药物基因组学和个性化医学”的年度会议。会议的目标是1)汇聚临床医生、基础和转化型科学家以及专职医疗从业者，开展多学科和跨学科的对话，以期在儿科环境中实施个性化药物；2)为介绍和传播与药物基因组学策略应用于儿童药物处置和反应的可变性研究有关的研究提供一个论坛；3)探讨药物基因组学和儿童特有的个性化药物的伦理、法律和社会影响；以及4)创造网络机会，鼓励讨论、合作和协作，以制定战略，满足确定的研究需求。归根结底，该计划的目标是提高所有年龄段儿童的药物安全性和有效性。 公共卫生相关性：一个专门关注儿科药物基因组学和个性化医学的会议将为有共同目标的临床医生和研究人员提供一个论坛，讨论这些问题，交流想法，建立合作和合作协议，对提高所有年龄和发育阶段儿童的药物安全性和有效性至关重要。

DESCRIPTION (provided by applicant): A major challenge for clinicians, pharmaceutical companies and regulatory agencies is to better understand the relative contributions of ontogeny and genetic variation to observed variability in drug disposition and response across the pediatric age spectrum from pre-term and term newborns, to infants, children and adolescents. Knowledge of the contribution of genetic variation to variability in drug disposition and response in adults has increased substantially over the past 25 years, but the application of pharmacogenetic and pharmacogenomic principles to pediatric drug therapy has lagged well behind. Extrapolation of adult experience with pharmacogenomics and personalized medicine to pediatric patients of different ages and developmental stages is fraught with many challenges. Some pediatric diseases have no adult correlate or are more prevalent in children compared to adults. Likewise, several adverse drug reactions are unique to children or occur at a higher frequency in children. Compared to adults, pediatric pharmacogenetics and pharmacogenomics involves an added measure of complexity as variability due to developmental processes, or ontogeny, is superimposed upon genetic variation. In the context of drug disposition and response, the additional complexity that ontogeny contributes manifests as unanticipated differences in dosing requirements, drug efficacy or risk of toxicity relative to what is expected based on experience in adults. The primary objective of this proposal is to establish an ongoing series of annual meetings on "Pediatric Pharmacogenomics and Personalized Medicine" organized by the Center for Personalized Medicine and Therapeutic Innovation and Division of Clinical Pharmacology and Medical Therapeutics at Children's Mercy Hospitals and Clinics in Kansas City, MO. The goals of the meeting are 1) To bring together clinicians, basic and translational scientists and allied healthcare practitioners, and engage in multi- and cross-disciplinary dialogue aimed at implementing personalized medicine in pediatric settings; 2) To provide a forum for the presentation and dissemination of research related to the application of pharmacogenomic strategies to investigations of variability of drug disposition and response in children; 3) To explore the ethical, legal and societal implications of pharmacogenomics and personalized medicine that are unique to children; and 4) To create networking opportunities for stimulating discussion, cooperation and collaboration to devise strategies to address research needs identified. Ultimately, the goal of this program is to improve the safety and efficacy of medications in children of all ages. PUBLIC HEALTH RELEVANCE: A meeting focused exclusively on Pediatric Pharmacogenomics and Personalized Medicine will provide clinicians and researchers who share a common goal of improving drug safety and efficacy in children a forum to discuss the issues, exchange ideas and establish collaborations and cooperative agreements critical to improving the safety and efficacy of medications in children of all ages and developmental stages.