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观察到的从早产儿和足月新生儿到婴儿、儿童和青少年的儿科年龄范围内药物处置和反应变异性的相对贡献。在过去的25年里，关于遗传变异对成人药物处置和反应的变异性的贡献的知识有了很大的增加，但是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中充满了许多挑战。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普遍。同样，一些药物不良反应是儿童独有的，或者在儿童中发生频率更高。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措施，因为发育过程或个体发育引起的变异性叠加在遗传变异上。在药物处置和反应的背景下，个体发育造成的额外复杂性表现为剂量要求、药物疗效或毒性风险相对于基于成人经验的预期差异的非预期差异。本提案的主要目的是继续由个性化医学和治疗创新中心以及密苏里州堪萨斯城儿童慈善医院和诊所的临床药理学和医学治疗学部门组织的“儿科药物基因组学和个性化医学”年度会议。会议的目标是1）汇集临床医生，基础和转化科学家和专职医疗从业人员，并参与旨在实施儿科环境个性化医疗的多学科和跨学科对话; 2）提供一个论坛，介绍和传播与药物基因组学策略应用相关的研究，以调查儿童药物处置和反应的变异性; 3）探讨药物基因组学和儿童特有的个性化医疗的伦理、法律的和社会影响; 4）创造网络机会，促进讨论、合作和协作，以制定战略，满足已确定的研究需求。最终，该计划的目标是提高所有年龄段儿童药物的安全性和有效性。

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 continue an ongoing series of annual conferences 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.