Arginine as Prophylactic Therapy in Sickle Cell Disease

描述（由申请人提供）： 本提案的目的是为洛里风格医学博士提供支持，以扩大她的临床研究调查，并加强她对新临床研究者的指导。Styles博士目前是NIH和FDA资助的积极临床研究者，支持镰状细胞病（SCD）中急性肺损伤和脑血管疾病的患者导向研究。该提案概述了一个正式的研究项目和指导计划。奥克兰儿童医院和研究中心的独特环境提供了一个理想的环境，通过提供大量的患者基础和实验室专业知识来实现这些目标。本申请中概述的研究计划描述了使用精氨酸作为预防性治疗以预防或减少SCD中血管闭塞事件的新临床研究。该项目源于一项正在进行的精氨酸治疗急性胸部综合征临床试验的结果，该试验证明精氨酸治疗可增加这些患者的一氧化氮产生并改善内皮功能障碍。本研究计划的具体目的是：1）全面评估SCD患者长期口服精氨酸的生理效应（有益和有害）; 2）评价每日口服精氨酸对SCD患者临床血管闭塞事件的影响。本提案中概述的临床试验和伴随的体外研究的成功完成将大大增加我们对口服精氨酸治疗SCD疗效的了解，并可能为这些患者带来有前途的新疗法。尽管忙碌临床研究生涯繁忙，斯泰尔斯博士已成功地指导了几个新的临床研究人员的道路上，一个独立的职业生涯。此应用程序概述了她的计划，继续和扩大她的指导作用与新的调查人员。Styles博士还计划开发一个新的临床奖学金计划，该计划将重点培训专门用于SCD临床研究的新研究人员。

DESCRIPTION (provided by applicant): The purpose of this proposal is to provide support for Lori Styles MD to expand her clinical research investigations and enhance her mentorship of new clinical investigators. Dr. Styles is presently an active clinical investigator with NIH and FDA funding supporting patient-oriented research in acute lung injury and cerebrovascular disease in sickle cell disease (SCD). This proposal outlines a formal research project and a plan for mentoring. The unique environment of Children's Hospital and Research Center at Oakland provides an ideal setting to accomplish these goals both through providing a large patient base and through laboratory expertise. The research plan outlined in this application describes a new clinical investigation of the use of arginine as a prophylactic treatment to prevent or reduce vaso-occlusive events in SCD. This project stems from results from an ongoing clinical trial of arginine in acute chest syndrome which has documented that treatment with arginine increases nitric oxide production and improves endothelial dysfunction in these patients. The specific aims of this research plan are 1) To comprehensively assess the physiological effects (both beneficial and deleterious) of the long term administration of oral arginine in patients with SCD and 2) To evaluate the effect of daily oral arginine on clinical vaso-occlusive events in SCD patients. Successful completion of the clinical trial and the accompanying in vitro investigations outlined in this proposal will substantially increase our knowledge about the efficacy of oral arginine as a therapy for SCD and could lead to a promising new therapy for these patients. Despite a busy clinical research career, Dr. Styles has successfully mentored several new clinical investigators on their way to an independent career. This application outlines her plans to continue and expand her mentorship role with new investigators. Dr. Styles also plans to develop a new clinical fellowship program which will focus on training new investigators specifically for clinical research in SCD.