Natural history of bone disease and the impact of growth hormone treatment in MPS

描述(由申请人提供)：波尔格林博士是明尼苏达大学内分泌学部儿科助理教授。自2008年8月开始担任这一职位以来，她将75%的时间投入到以患者为导向的儿科骨病领域的研究，并将在这一职业发展获奖期间继续这样做。波尔格林博士的长期职业目标是成为一名独立的学术内科研究员，在粘多糖症(MPS)儿童的儿科骨骼和内分泌疾病领域拥有国际公认的专业知识。在此授奖期间要实现的具体目标包括：1)提高基础骨生物学、骨评估方法和临床试验管理方面的知识；2)完成一项临床试验，并对MPS的骨和内分泌疾病进行纵向研究。虽然接受造血细胞移植(HCT)和/或酶替代疗法(ERT)治疗的MPS I、II和VI儿童可以活到成年期，但他们的认知结果良好，但他们的生活质量受到持续性骨骼异常、肌挛缩和严重矮小的显著影响。在项目发起人切斯特·惠特利博士的指导下，波尔格林博士将追求以下具体目标：1)采用2/3期随机对照试验设计，确定24个月的重组人生长激素治疗与不治疗对34名患有MPS I、II和VI且身材矮小的儿童骨骼发育和生长的影响；2)采用为期3年的前瞻性研究设计，通过外周定量计算机断层扫描(PQCT)、双能X射线吸收测量仪(DXA)、骨代谢生物标志物和内分泌功能实验室测试，对患有MPS I、II和VI的儿童的骨发育(骨密度、几何形状和估计强度)和内分泌功能进行登记。这些研究项目和职业发展将在以下指导团队的指导下进行：切斯特·惠特利博士、安托瓦内特·莫兰博士、莫伊拉·佩蒂特博士和威廉·托马斯博士。该团队在罕见疾病研究(Whitley)、临床试验管理(Moran)、儿科骨骼评估理论和方法(Petit)以及生物统计学(Thomas)等领域提供专业知识。在MPS和儿科骨病方面的丰富经验，以及在密歇根大学跟随的大量MPS儿童，使这里成为Polgreen博士研究和职业发展成为儿科代谢性骨病独立研究员的理想环境。

DESCRIPTION (provided by applicant): Dr. Polgreen is an Assistant Professor in the Department of Pediatrics, Division of Endocrinology, at the University of Minnesota (UM). Since starting in this position in August 2008, she has devoted 75% of her time to patient-oriented research in the field of pediatric bone disease and will continue this during this career development award period. Dr. Polgreen's long-term career goal is to become an independent academic physician researcher, with internationally recognized expertise in the area of pediatric bone and endocrine disease in children with mucopolysaccharidoses (MPS). Specific goals to be accomplished during this award period include: 1) improve knowledge in basic bone biology, bone assessment methodology, and clinical trials management; 2) completion of a clinical trial and a longitudinal study of bone and endocrine disease in MPS. Although children with MPS I, II, and VI who are treated with hematopoietic cell transplantation (HCT) and/or enzyme replacement therapy (ERT) are living into adulthood with good cognitive outcomes, their quality of life is significantly impacted by their persistent skeletal abnormalities, contractures, and severe short stature. Under the guidance of Dr. Chester Whitley, the project sponsor, Dr. Polgreen will pursue the following specific aims: 1) To determine the impact of 24 months of recombinant human growth hormone therapy versus no therapy on bone development and growth in 34 children with MPS I, II, and VI and short stature with a Phase 2/3 randomized controlled trial design; 2) To develop a registry of bone development (bone density, geometry, and estimated strength) and endocrine function in children with MPS I, II, and VI using a 3-year prospective study design with yearly evaluations with peripheral quantitative computer tomography (pQCT), dual energy x- ray absorptiometry (DXA), biomarkers of bone metabolism, and laboratory tests of endocrine function. These research projects and career development will be conducted under the guidance of the following mentorship team: Dr. Chester Whitley, Dr. Antoinette Moran, Dr. Moira Petit, and Dr. William Thomas. This team provides expertise in the areas of the study of rare disease (Whitley), clinical trials management (Moran), theories and methods of bone assessment in pediatrics (Petit), and biostatistics (Thomas). The extensive experience with MPS and pediatric bone disease, and the large cohort of children with MPS followed at UM, make this the ideal environment for Dr. Polgreen's research and career development into an independent investigator of pediatric metabolic bone disease.