Lysosomal Disease Network

描述(申请人提供)：虽然个别罕见的“孤儿”情况，溶酶体疾病共同影响1/6,000人，并负责重大残疾和疾病负担。这些疾病已经成为一些最具创新性和最先进的实验性治疗的试验台。每种溶酶体疾病的罕见意味着，没有一个医学研究中心有机会看到整个谱系，也没有机会获得足够的数据来充分测试新的治疗方法。因此，对这些罕见疾病及其治疗进行协作临床研究对于取得实质性进展绝对至关重要。溶酶体疾病网络汇集了全国500多名研究人员和临床医生、患者倡导团体(PAG)和其他感兴趣的合作伙伴，并产生了一个协同研究和教育联盟，以推进这些疾病的治疗。在这项建议中，11种溶酶体疾病的自然历史的纵向研究和7项结果测量和L/11期临床试验的试点研究集中在几个主题上。中枢神经系统(CNS)疾病一直是最难治疗和测量的疾病。重点将放在对中枢神经系统结构和功能的定量方法上，为粘多糖病(MPS)、巴顿病、Niemann-Pick C型、IV型粘膜脂沉积症、晚期婴儿神经元性Ceroid脂褐素沉着症、糖蛋白增多症、GM2神经节苷脂增多症和Wolman病提供一个标准工具箱。庞培病的研究主要集中在影响治疗反应的免疫调节因素上。此外，我们还在MPS中进行了一项关于骨病的研究，以及一系列关于Fabry病的创新研究，在这些研究中，合作者将进行肾脏结构和功能的自然病史、作为儿童疾病进展标志的肺功能，以及在高危人群中识别Fabry病。我们将为所有这些项目提供支持，利用PAG和工业界的额外资源，希望促进对其他溶酶体疾病的研究，并推动对病理生理和治疗的更深入研究。此外，该网络将为每年至少两名溶酶体病职业发展的博士后实习生提供实质性支持，并为分享研究成果、教育和网络协同作用的全国会议(世界研讨会)提供实质性支持。网站www.LysosomalDiseaseNetwork.org已经为该网络、患者、医生和公众提供了教育、研究和临床资源。公共卫生相关性：溶酶体疾病网络的联合和综合努力将集中有限的资源，以创建一个拥有一种或多种此类疾病专业知识的中心网络，以解决诊断、疾病管理和治疗方面的重大挑战。这些问题的解决将直接影响到患有溶酶体疾病的患者，并对医疗实践具有重要意义。

DESCRIPTION (provided by applicant): Although individually rare "orphan" conditions, the lysosomal diseases collectively affect 1 in 6,000 individuals and are responsible for a significant disability and disease burden. These diseases have become a test bed for some of the most innovative and advanced experimental treatments. The rarity of each lysosomal disease means that no single medical research center has an opportunity to see the entire spectrum, or to acquire sufficient numbers to adequately test new therapies. Thus, collaborative clinical research on these rare disorders and their treatment is absolutely crucial to make substantial progress. The Lysosomal Disease Network brings together more than 500 researchers and clinicians across the country, Patient Advocacy Groups (PAG), and other interested partners, and has generated a synergistic research and educational consortium to advance treatment of these diseases. In this proposal, longitudinal studies of the natural history of 11 lysosomal disease categories and 7 pilot studies of measurement of outcome and phase l/ll clinical trials are focused on several themes. Central nervous system (CNS) disease has been the most difficult to treat as well as to measure. A significant focus will be on quantitative methods of CNS structure and function providing a standard toolbox across the network in the Mucopolysaccharidoses (MPS), Batten disease, Niemann-Pick type C, Mucolipidosis type IV, Late Infantile Neuronal Ceroid Lipofuscinosis, Glycoproteinoses, GM2-gangliosidoses, and Wolman disease. A study on Pompe disease focuses primarily on the immune modulatory factors affecting treatment response. Additionally, we include a study on bone disease in the MPS and a set of innovative studies on Fabry disease in which collaborators will carry out the natural history of kidney structure and function, pulmonary function as a marker of disease progression in children, and identification of Fabry disease among high-risk populations. We will provide support for all of these projects, leveraging additional resources from PAG and industry, in the hope of fostering research on other lysosomal diseases and providing the impetus for more in-depth studies of pathophysiology and treatment. In addition, this network will provide substantial support for at least two postdoctoral trainees each year for career development in lysosomal diseases as well as a national meeting (WORLD Symposium) for sharing of research findings, education, and network synergy. A web-site www.LysosomalDiseaseNetwork.org already provides an educational, research, and clinical resource for the Network, patients, physicians, and the public. PUBLIC HEALTH RELEVANCE: The combined and integrated efforts of the Lysosomal Disease Network will focus limited resources toward creating a network of centers with expertise in one or more of these diseases in order to solve major challenges in diagnosis, disease management, and therapy. Solutions to these problems will have direct impact on patients suffering from lysosomal diseases, and important implications for medical practice.