Hinxton Conference of Excellence - Dense Deposit Disease: Therapeutic Options

描述(由申请人提供)： 第三届致密沉积疾病国际会议(DDD，也称为膜增生性肾小球肾炎II型或MPGN II)将于2008年8月15日至17日在英国欣克斯顿基因组校园的桑格中心举行，作为欣克斯顿卓越会议。这次会议的目的和目标是：1)介绍我们对DDD发病机制的理解进展，因为这些进展与开发适合DDD的治疗方法有关；2)介绍动物研究的数据，因为这些数据与使用DDD的小鼠模型快速评估体内潜在治疗方法有关；3)确定、定义和解决在未来1-2年内开始DDD临床试验必须考虑的问题。这些目的和目标是前两次有关DDD的国际会议的合乎逻辑的延伸，并将通过以下方式实现：1)汇聚在补体替代途径方面有专长的临床医生和基础科学家；在DDD方面有专长的肾脏病理学家；在肾小球肾炎和临床试验方面有专长的临床肾科医生；在DDD方面有专长的遗传学家；以及在糖胺聚糖和肾小球基底膜(GBM)方面有专长的生物化学家；2)集中研究导致DDD的致病机制，特别是最近发现的与C3b，特别是IC3b、C3dg和C3c有关的分解产物，它们是导致致密沉积物形成的蛋白质；3)根据血清C3b/IC3b、C3dg和C3c的比值，重点实施新的临床相关和特异的DDD诊断试验；4)探索我们对DDD作为一种复杂疾病的理解的遗传进展，以及DDD患者携带的遗传风险等位基因数量与进展为终末期肾功能衰竭的可能性之间的关系；5)审查最近开发的在线数据库密集沉积疾病结局数据库(DDDOD)，该数据库允许以符合HIPPA的格式输入全球患者数据，并促进结果报告，从而为原本可能在一生中只治疗一到两例DDD的临床医生提供针对多个病例的虚拟实时体验；6)审查目前唯一可用的使用舒洛地特进行的DDD临床试验(1期试验；ClinicalTrials.gov标识NCT00583427)；7)审查研究设计，认识到由于DDD是一种罕见疾病，随机对照设计可能不适合。前两次会议的结果发表在《美国肾病学会杂志》(Appl等人，2005年；Smith等人，2007年)上，并对DDD患者的护理产生了影响。我们还将发表这次会议的会议记录，并希望这份出版物将促进人们对开发针对DDD的治疗方法来治疗这种疾病的持续兴趣。

DESCRIPTION (provided by applicant): The third international conference on Dense Deposit Disease (DDD, also known as Membranoproliferative Glomerulonephritis Type II or MPGN II) will be held August 15-17, 2008 as a Hinxton Conference of Excellence at the Sanger Centre on the Genome Campus, Hinxton, England. The aims and objectives of this meeting are: 1) To present advances in our understanding of the pathogenesis of DDD as these advances relate to the development of DDD-appropriate therapies; 2) To present data from animal studies as these data relate to the use of a murine model of DDD to rapidly evaluate potential therapies in vivo; 3) To identify, define and address issues that must be considered to begin clinical trials for DDD in the next 1-2 years. These aims and objectives are a logical extension of the first two international conference on DDD and will be achieved by: 1) Bringing together clinicians and basic scientists with expertise in alternative pathway of complement; nephropathologists with expertise in DDD; clinical nephrologists with expertise in glomerulonephritis and clinical trials; geneticists with expertise in DDD; and biochemists with expertise in glycosaminoglycans and the glomerular basement membrane (GBM); 2) Focusing on the pathogenic mechanisms that lead to DDD, with special emphasis on recent discoveries that implicate breakdown products of C3b, in particular iC3b, C3dg and C3c, as proteins that lead to formation of the dense deposits; 3) Focusing on the implementation of novel clinically relevant and specific diagnostic tests for DDD based on the serum ratio of C3b to iC3b, C3dg and C3c; 4) Exploring genetic advances in our understanding of DDD as a complex disease and how the number of genetic risk alleles a patient with DDD carries correlates with the likelihood of progressing to end-stage renal failure; 5) Reviewing a recently developed on-line database, the Dense Deposit Disease Outcomes Database (DDDOD), that permits global entry of patient data in a HIPPA-compliant format and facilitates outcomes reporting thereby providing clinicians who may otherwise treat only one or two cases of DDD in a lifetime a virtual real-time experience with multiple cases; 6) Reviewing the only current available clinical trial for DDD using Sulodexide (a Phase 1 trial; ClinicalTrials.gov Identifier NCT00583427) as a model for clinical trials using other agents; 7) Reviewing study trial design, recognizing that because DDD is a rare disease, a randomized control design may not be suitable. The outcomes of the first two meeting were published in the Journal of the American Society of Nephrology (Appel et al., 2005; Smith et al., 2007) and have impacted the care of patients with DDD. We will also publish the proceedings of this meeting and hope this publication will foster continued interest in developing DDD-specific therapies to treat patients with this disease.