Autonomic Rare Diseases Clinical Research Consortium

描述(申请人提供)：自主神经罕见病临床研究联盟 我们提出了一个自主的RDCRC，由NHLBI/NINDS支持的范德比尔特、梅奥、纽约大学、哈佛大学和NINDS内部计划的调查人员组成。如果RDCRC获奖，我们希望利用杠杆资金扩大到更多的地点。自主神经障碍的4个主要支持团体也是该联盟的参与者。我们的目标是研究自主神经障碍，以便我们能够开发新的治疗方法，目的不仅是改善生活质量，而且还可以改变疾病的进程。这种自主的RDCRC是多学科的，得到了我们患者及其支持组织的大力支持。我们的战略是通过自然历史研究、治疗试验、患者登记和数据/样本库来实现我们的目标。我们将培训医生和科学家进行罕见自主神经疾病的调查和治疗。我们将开发一个自主精神障碍网站，以加强患者、患者家属、支持团体和公众之间的沟通。我们最初关注四种罕见且难治的自主神经疾病，其特征是改变生活的残疾：(1)多系统萎缩，MSA；(2)单纯自主神经衰竭；(3)自身免疫性自主神经节病；(4)低容量体位性心动过速综合征。我们提出的新干预措施包括去甲肾上腺素转运阻滞剂、多巴脱羧酶拮抗剂、免疫调节疗法、仿生压力感受器反射，以及对一致致命的MSA进行潜在的疾病休息干预。我们联盟的几个功能将有助于我们发现独特的遗传或获得性病理生理学。该联盟成员还正在进行本提案中没有描述的针对其他罕见自主神经障碍的病理生理学和治疗研究，例如(1)家族性自主神经功能障碍(2)多巴胺β-羟基酶缺乏，(3)压力反射衰竭，(4)去甲肾上腺素转运体缺乏。联盟成员相信，自主的RDCRC将真正改变受影响患者的生活。公共卫生相关性：自主神经障碍导致心脏、血管、胃、肠道和膀胱失去调节。受影响的患者经常出现心悸或失去意识，有些人的病程很快就会致命。自主联盟建议与患者支持团体一起，利用这些患者所在的主要中心的医生和研究人员的知识和精力，以便他们能够找到治疗和治愈这些疾病的方法

DESCRIPTION (provided by applicant): Autonomic Rare Disease Clinical Research Consortium We propose an Autonomic RDCRC comprising NHLBI/NINDS-supported investigators at Vanderbilt, Mayo, New York University, Harvard, and the NINDS Intramural Program. If this RDCRC is awarded, we hope to expand to additional sites with leveraging funds. The 4 major support groups for autonomic disorders are also participants in the Consortium. Our objective is to study autonomic disorders so that we can develop novel therapies aimed not only at improving quality of life, but also altering the course of disease. This Autonomic RDCRC is multidisciplinary and draws strong support from our patients and their support organizations. Our strategy is to meet our goals through natural history studies, therapeutic trials, patient registries, and data/specimen banks. We will train physicians and scientists in the investigation and treatment of rare autonomic disorders. We will develop an Autonomic Disorders Web Site to enhance communication among patients, families, support groups and the general public. We focus initially on four rare and intractable autonomic disorders characterized by life-altering disability: (1) multiple system atrophy, MSA; (2) pure autonomic failure; (3) autoimmune autonomic gangljonopathy; and (4) hypovolemic postural tachycardia syndrome. Our proposed novel interventions include a norepinephrine transport blocker, a dopa decarboxylase antagonist, immunomodulatory therapy, a bionic baroreflex, and a potentially diseasearresting intervention in the uniformly fatal MSA. Several features of our Consortium will facilitate our ability to discover unique genetic or acquired pathophysiologies. Consortium members also have ongoing pathophysiologic and therapeutic studies, not described in this proposal, aimed at other rare autonomic disorders such as (1) familial dysautonomia (2) dopamine beta-hydroxylase deficiency, (3) baroreflex failure, and (4) norepinephrine transporter deficiency. The Consortium members believe that the Autonomic RDCRC will make a real difference in the lives of affected patients. PUBLIC HEALTH RELEVANCE: Autonomic disorders cause loss of regulation of the heart, blood vessels, stomach, bowel and bladder. Affected patients frequently have palpitations or lose consciousness, and some have a rapidly fatal course. The Autonomic Consortium proposes to join with patient support groups to harness the knowledge and energies of physicians and investigators in the major centers where these patients are cared for, so that they can discover ways to treat and to cure these diseases