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

描述(申请人提供)：我们寻求支持罕见肺部疾病临床研究联盟(RLDC)，促进一组罕见肺部疾病的临床研究、培训和教育，基于分子通路驱动的新诊断和治疗方法的发展。拟议的具体目标包括1)建立一个专注于淋巴管肌瘤病(LAM)、肺泡蛋白沉着症(PAP)和Hermansky-Pudlak综合征(HPS)的联盟，2)在最初通过LAM诊所建立的海外罕见肺部疾病临床中心网络中进行与LAM、PAP和HPS相关的纵向和治疗性临床研究，3)进行试点和示范计划，以开发和评估这些和其他‘甲板上’罕见肺部疾病的新诊断、治疗和结果措施，4)在RLDC临床中心提供临床研究培训，并吸引新的研究人员到该领域，以及5)为患者开发罕见肺部疾病教育材料，医疗提供者和公众。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记物和诊断测试，以及评估每种疾病的自然病史。我们建立在以往成功经验的基础上，包括开发新的诊断方法(在PAP和LAM)，通过RLDC进行的第一个成功的LAM治疗试验(‘迈尔斯’)，与患者权益倡导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(包括一名前实习生，现为该应用程序的项目负责人)。该网络包括辛辛那提儿童中心(协调中心)、俄亥俄州辛辛那提大学(联席董事)和范德比尔特的三个翻译站点，以及从“现有LAM诊所网络”中挑选出来的临床研究站点。参与的患者支持团体包括LAM基金会、PAP基金会、HPS Network和Alpha-1基金会。这些中心和基金会已经与从活跃的协作临床中心网络中选择的临床地点紧密结合在一起，该网络包括分布在美国各地的22个州的28个地点。参与的翻译中心将利用现有NIH临床和翻译科学奖(CTSA)的资源，以及包括儿科机会在内的种族多元化人口。每个中心都提供持续的纵向临床研究，出色的临床培训计划， 以及旨在测试新疗法、开发诊断测试和评估结果衡量标准的积极临床计划，这些措施将导致新的治疗方法并改善患者的生活

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