Lysosomal Disease Network

描述（由申请人提供）：尽管个别罕见的“孤儿”病症，溶酶体疾病总体影响6,000人中有1人，并造成严重的残疾和疾病负担。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。每一种溶酶体疾病都很罕见，这意味着没有一个医学研究中心有机会看到整个谱系，或者获得足够的数量来充分测试新的疗法。因此，对这些罕见疾病及其治疗的合作临床研究对于取得实质性进展至关重要。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，并形成了一个协同研究和教育联盟，以推进这些疾病的治疗。在本提案中，对11种溶酶体疾病类别的自然史进行纵向研究，对结果测量和i /ll期临床试验进行7项试点研究，重点关注几个主题。中枢神经系统（CNS）疾病一直是最难治疗和测量的疾病。重点将是CNS结构和功能的定量方法，为粘多糖病（MPS）、Batten病、Niemann-Pick C型、粘脂病IV型、晚期婴儿神经元类脂褐质病、糖蛋白病、gm2神经节脂质剂量和Wolman病提供一个跨网络的标准工具箱。对庞贝病的研究主要集中在影响治疗反应的免疫调节因子上。此外，我们还包括一项关于MPS骨病的研究和一系列关于法布里病的创新研究，其中合作者将开展肾脏结构和功能的自然史，肺功能作为儿童疾病进展的标志，以及在高危人群中识别法布里病。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，并为更深入的病理生理学和治疗研究提供动力。此外，该网络每年将为至少两名博士后培训生提供大量支持，以促进溶酶体疾病的职业发展，并为分享研究成果、教育和网络协同作用提供一次全国会议（世界研讨会）。一个网站www.LysosomalDiseaseNetwork.org已经为网络、病人、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把有限的资源集中在创建一个具有一种或多种这些疾病专业知识的中心网络上，以解决诊断、疾病管理和治疗方面的主要挑战。这些问题的解决将对溶酶体疾病患者产生直接影响，并对医疗实践产生重要影响。

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.