CLINICAL RESEARCH IN PEDIATRIC SICKLE CELL DISEASE

细胞疾病的临床研究已经达到了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疾病领域出类拔萃的临床研究人员。布里吉塔·U·穆勒博士是成长为这一角色的理想人选。她是一名儿科血液学家/肿瘤学家，早期在国家癌症研究所(NCI)的内科项目中专注于与儿科艾滋病毒疾病相关的临床试验。我们已经将她招募到儿童医院，这样她就可以将注意力转移到镰状细胞疾病上，同时扩大她的培训和临床研究经验。我们五年发展计划的目标是让她成为一名独立研究员-领导我们机构的镰状细胞临床研究，并指导多机构研究。米勒博士将在奥拉·S·普拉特博士和卡洛·布鲁格纳拉博士的指导下继续她的职业发展。普拉特博士是一名经验丰富的镰状细胞疾病研究人员，卡洛·布鲁格纳拉博士是设计镰状细胞疾病创新疗法的专家。她将把她的努力集中在四个主要领域：1)在5年内，她将与普拉特博士一起看望和讨论患者，并与布鲁格纳拉博士会面，讨论研究想法和审查数据。2)她将进行和分析拟议的临床试验-评估已知的钾-氯共转运抑制剂镁对Hb-SC病患者的效果。我们的假设是，口服镁将阻断钾-氯共转运，防止细胞脱水，并减少聚合诱导的血管闭塞并发症。3)她将设计和实施一个研究基础设施，作为未来提案的资源。4)她将在哈佛大学公共卫生学院完成课程工作，并获得公共卫生硕士学位，专注于研究设计、实施和分析。我们建议的镁预防Hb SC病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投入临床试验的模板。

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.