Arginine as Prophylactic Therapy in Sickle Cell Disease

描述(由申请人提供)： 这项建议的目的是为Lori Styles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人员的指导。Styles博士目前是一名活跃的临床研究员，由NIH和FDA资助，支持以患者为导向的镰状细胞病(SCD)急性肺损伤和脑血管疾病研究。这份提案概述了一个正式的研究项目和一个指导计划。奥克兰儿童医院和研究中心的独特环境为实现这些目标提供了理想的环境，既提供了大量的患者基础，也提供了实验室专业知识。本申请中概述的研究计划描述了一项新的临床研究，即使用精氨酸作为预防治疗来预防或减少SCD的血管闭塞事件。该项目源于正在进行的精氨酸治疗急性胸部综合征的临床试验的结果，该试验证明，精氨酸治疗增加了这些患者的一氧化氮产生并改善了内皮功能障碍。这项研究计划的具体目的是：1)全面评估长期口服精氨酸对SCD患者的生理影响(包括有益和有害的)；2)评估每日口服精氨酸对SCD患者临床血管闭塞事件的影响。这项提案中概述的临床试验和随之而来的体外研究的成功完成将大大增加我们对口服精氨酸作为SCD疗法的有效性的了解，并可能为这些患者带来一种有前景的新疗法。尽管斯泰尔斯博士的临床研究生涯十分繁忙，但他已经成功地指导了几位即将迈向独立职业生涯的新临床研究人员。这份申请概述了她继续和扩大她在新调查人员中的指导角色的计划。Styles博士还计划开发一项新的临床研究计划，该计划将侧重于培训专门用于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.