RLDC: Molecular Pathway-Driven Diagnostics & Therapeutics for Rare Lung Diseases

描述（由申请人提供）：我们寻求罕见肺病临床研究联盟（RLDC）的支持，以促进基于分子途径驱动的新型诊断和治疗方法开发的一组罕见肺病的临床研究，培训和教育。提出的具体目标包括：1)建立一个专注于淋巴血管平滑肌瘤病（LAM）、肺泡蛋白沉积症（PAP）和Hermansky-Pudlak综合征（HPS）的联盟；2)在最初通过LAM诊所建立的国外罕见肺病临床中心网络中开展与LAM、PAP和HPS相关的纵向和治疗性临床研究；3)开展一项试点和示范项目，以开发和评估新的诊断、治疗方法。4)在RLDC临床中心提供临床研究培训，并吸引新的研究人员进入该领域；5)为患者、医疗提供者和公众开发罕见肺病教育材料。疾病之间的协同作用包括使用定量放射结果评估，强调开发和评估基于血液的生物标志物和诊断测试，以及评估每种疾病的自然史。我们建立在先前的成功基础上，包括开发新的诊断方法（PAP和LAM），通过RLDC（“MILES”）进行的首次成功的LAM治疗试验，与患者权益团体的长期合作伙伴关系，以及罕见肺部疾病的培训和职业发展记录（包括一位前实习生，现在是该应用程序的项目负责人）。该网络由辛辛那提儿童医院（协调中心）、俄亥俄州辛辛那提市辛辛那提大学（联合主管）和范德比尔特大学的三个翻译站点以及从“现有LAM诊所网络”中选择的临床研究站点组成。参与的患者支持团体包括LAM基金会、PAP基金会、HPS网络和Alpha-1基金会。这些中心和基金会已经与从活跃的合作临床中心网络中选择的临床站点紧密结合，这些合作临床中心包括分布在美国22个州的28个站点。参与的转化中心将利用现有的NIH临床和转化科学奖（CTSA）和包括儿科机会在内的种族多样化人口的资源。每个中心都提供持续的纵向临床研究，优秀的临床培训项目，

DESCRIPTION (provided by applicant): We seek support for a Rare Lung Diseases clinical research Consortium (RLDC) facilitating clinical research, training, and education for a group of rare lung diseases based on molecular pathway-driven development of novel diagnostics and therapeutics. The proposed Specific Aims include 1) establish a Consortium focused to Lymphangioleiomyomatosis (LAM), Pulmonary Alveolar Proteinosis (PAP), and Hermansky-Pudlak Syndrome (HPS), 2) conduct longitudinal and therapeutic clinical studies related to LAM, PAP, and HPS at abroad network of rare lung disease clinical centers established initially via LAM clinics, 3) conduct of a Pilot and Demonstration program for the development and evaluation of novel diagnostics, therapeutics, and outcome measures for these and additional 'on-deck' rare lung diseases, 4) provide clinical research training at RLDC clinical centers and attract new investigators to the field, and 5) develop rare lung disease educational materials for patients, medical providers, and the public. Synergies between diseases include the use of quantitative radiological outcome assessment, an emphasis on development and evaluation of blood-based biomarkers and diagnostic tests, and the evaluation of the natural history of each disease. We build on prior successes including development of novel diagnostics (in PAP and LAM), the first successful therapeutic trial for LAM conducted through the RLDC ('MILES'), longstanding partnerships with patient advocacy groups, and a track record of training and career development in rare lung diseases (including a former trainee who is now a project leader in this application). The network consists of three translational sites at Cincinnati Children's (the coordinating center), the University of Cincinnati in Cincinnati, Ohio (a co-directorship), and Vanderbilt, and clinical research sites selected from the "existing LAM Clinic Network. Participating patient support groups include the LAM Foundation, PAP Foundation, HPS Network, and the Alpha-1 Foundation. These centers and Foundations are already closely integrated with clinical sites chosen from active networks of collaborating clinical centers that include over 28 sites in 22 states distributed throughout the United States. Participating translational centers will leverage resources from existing NIH Clinical and Translational Science Awards (CTSA) and a racially diverse population that includes pediatric opportunities. Each center provides ongoing longitudinal clinical studies, an excellent clinical training program, and active clinical programs designed to test novel therapies, develop diagnostic tests and evaluate outcome measures that will lead to new therapies and improve the lives of affected