Rare Disease Research Platform: The renal ciliopathies national network (RCNN)

肾纤毛病是一种罕见的遗传性肾脏疾病，约占所有肾衰竭患者的10%，这些患者需要透析和肾移植等专科治疗。现代遗传学和细胞生物学现在让我们对这组疾病有了一些重要的认识。最常见的形式被称为常染色体显性多囊肾病，最近第一批药物已经进入临床，以减缓这种疾病。目前仍缺乏预防或消除这种疾病的治疗方法。这一罕见疾病的患者群体相对较大，有数千名患者受到影响，对我们的卫生保健系统来说是一个重大的未满足的挑战。他们也为英国国内的创新和投资提供了一个重要的机会，比如我们成为世界领导者。我们相信，通过调整这些患者队列，利用我们在分子诊断、深度临床表型和疾病建模方面的专业知识，我们可以加速新疗法的开发。在这里，我们将为对肾纤毛病感兴趣的临床医生和科学家创建一个可访问的多机构，多学科的合作网络。我们将促进来自全国各地的临床和研究团队的集体参与，并确保合作伙伴之间有效的数据共享。通过将不同的肾纤毛病患者聚集在一个网络中，我们可以利用人类疾病遗传学对变异和基因如何控制肾脏功能和疾病进展的最大理解。我们将开发强大的基于患者来源的细胞功能分析，以了解疾病机制，并快速发现肾纤毛病急需的治疗方法。肾纤毛病国家网络（RCNN）旨在：协调临床、影像学和分子遗传学检查作为英国所有肾纤毛病患者的标准；改进对潜在遗传变异的基因组解释，发展具有良好特征的患者群体，为新的个性化药物治疗试验做好准备。在此过程中，我们将通过与患者团体和慈善机构的合作，建立一个支持纤毛病患者及其家属的国家系统，更好地与临床护理团队和研究人员交流，而不考虑邮政编码。我们相信，让患者参与塑造肾纤毛病转化景观的这些早期步骤，将导致更好的设计试验，并确定对我们的患者有意义的终点。我们相信，MRC/NIHR罕见病投资创建RCNN将有助于与全国护理团队建立强大的临床联系，促进行业与我们的患者倡导团体之间建立有意义的合作关系，并创造机会倡导重大行业投资，以加速肾纤毛病新疗法的开发。总之，RCNN的目标是改善全国范围内肾纤毛病患者的护理，为“准备好试验”的分层患者群体开发基础设施，并与学术界和工业界建立伙伴关系，以加速急需的新疗法的开发。

A group of rare inherited kidney diseases known as renal ciliopathies represent around 10% of all patients with kidney failure, who need specialist treatments including dialysis and kidney transplantation. Modern genetics and cell biology has now allowed us some important insights into this group of diseases. The most commonly seen form is called autosomal dominant polycystic kidney disease and recently the first drugs have come to the clinic to slow down this disease. Treatments that prevent or switch off the disease are still lacking. This group of patients with rare disease is relatively large with several thousand patients affected and are significant unmet challenge for our health care system. They also present a significant opportunity for innovation and investment within the UK such as we become world leaders. We believe that by aligning these patient cohorts to exploit our expertise in molecular diagnostics, deep clinical phenotyping and disease modelling we can accelerate development of novel treatments. Here, we will create an accessible multi-institutional, multi-disciplinary collaborative network for both clinicians and scientists interested in the renal ciliopathies. We will foster the collective engagement of clinical and research teams from across the country, and ensure efficient data sharing between partners. By bringing together different renal ciliopathy disease patients within one network, we can harness the most understanding from our human disease genetics as to how variants and genes control kidney function and disease progression. We will develop powerful patient-derived cell-based functional assays to understand disease mechanisms and to fast-track discovery of much needed therapeutics in the renal ciliopathies. The renal ciliopathies national network (RCNN) aims to: harmonise clinical, imaging and molecular genetic work-up as standard for all renal ciliopathy patients in the UK; improve genomic interpretation of underlying genetic variants and develop well characterised groups of patients who are trial ready for new personalised medicine treatments. In doing so, we will create a national system of support for ciliopathy patients and their families through partnerships with patient groups and charities, better interfaced with clinical care teams and researchers regardless of postal code. We believe that involving patients in these early steps of shaping the translational landscape for renal ciliopathies as we move forward will lead to better designed trials and identifying endpoints that would be meaningful for our patients.We believe that MRC/NIHR Rare Disease investment to create the RCNN would help build strong clinical links to care teams nationally, foster successful relationships between industry and our patient advocacy groups to establish meaningful collaborations, and create the opportunity to advocate for significant industry investment to accelerate development of new treatments for the renal ciliopathies. In summary, the RCNN aims to improve renal ciliopathy patient care nationwide, to develop infrastructure for stratified patient cohorts that are 'trial-ready' and build partnerships with academics and industry to accelerate development of much-needed new treatments.