CLINICAL RESEARCH IN PEDIATRIC SICKLE CELL DISEASE

细胞病（SCD）的临床研究已达到一个新的发展里程碑。具有讽刺意味的是，最近羟基脲和其他新疗法的成功使临床研究工作变得更加困难。为了推动这一领域的发展，我们现在需要培养在临床研究和镰状细胞病领域表现出色的临床研究者。布丽吉塔·穆勒博士是这个角色的理想人选。她是一名儿科血液学家/肿瘤学家，早期在美国国家癌症研究所（NCI）的校内项目中专注于与儿科HIV疾病相关的临床试验。我们将她招募到儿童医院，以便她可以将注意力转移到镰状细胞病上，同时扩大她在临床研究方面的培训和经验。我们五年发展计划的目标是让她成为一名独立的研究者，领导我们机构的镰状细胞临床研究，并指导多机构研究。她将在镰状细胞病经验丰富的研究者Orah S. Platt博士和镰状细胞病创新疗法设计专家Carlo Brugnara博士的指导下追求她的职业发展。她将集中精力在四个主要领域：1)在5年的时间里，她将与Platt博士一起观察和讨论患者，并与Brugnara博士会面讨论研究思路和审查数据。2)她将进行并分析拟议的临床试验-评估Mg（一种已知的K-Cl共转运抑制剂）在Hb SC患者中的作用。我们的假设是口服Mg会阻断K- Cl共转运，防止细胞脱水，减少聚合诱导的血管闭塞性并发症。她将设计并实施一个研究基础设施，作为未来提案的资源。4)在哈佛大学公共卫生学院完成课程学习并取得公共卫生硕士学位，专注于研究设计、实施；和分析。我们提出的Mg预防Hb SC患者疼痛危机的试验，将作为将基础实验室设计的各种治疗方法引入临床试验的模板。

Clinical research in cell disease (SCD) has reached a new developmental milestone. Ironically, the recent success of hydroxyurea and other new treatments makes the work of clinical investigation harder. In order to move the field forward, we now need to develop clinical investigators who excel in the arenas of clinical investigation and sickle cell disease. Dr. Brigitta U. Mueller is an ideal person to grow into this role. She is a pediatric hematologist/oncologist who early on focused on clinical trials related to pediatric HIV disease at the National Cancer Institute's (NCI) intramural program. We have recruited her to Children's Hospital so that she can shift her attention to sickle cell disease while expanding her training and experience in clinical investigation. The goal of our five-year development plan is for her to become an independent investigator - lead sickle cell clinical research at our institution, and direct multi-institutional studies. Dr. Mueller will pursue her career development under the mentorship of Dr. Orah S. Platt, an experienced investigator in sickle cell disease, and Dr. Carlo Brugnara, an expert in design of innovative therapies in sickle cell disease. She will focus her efforts in four major areas: 1) Throughout the 5 years she will see and discuss patients with Dr. Platt, and meet with Dr. Brugnara to discuss research ideas and review data. 2) She will conduct and analyze the proposed clinical trial - evaluating the effect of Mg, a known inhibitor of K-Cl cotransport, in patients with Hb SC disease. Our hypothesis is that oral Mg will block K- Cl cotransport, prevent cell dehydration, and reduce polymerization-induced vasoocclusive complications. 3) She will design and implement a research infrastructure that will be used as a resource for future proposals. 4) She will do course work at the Harvard School of Public Health and obtain the MPH degree, concentrating on research design, implementation; and analysis. The trial of Mg for the prevention of pain crises in patients with Hb SC disease that we propose, will serve as a template for bringing a variety of treatments designed in basic laboratories to clinical trial.