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

罕见疾病研究平台：肾纤毛病国家网络 (RCNN)

• 批准号: MR/Y007808/1
• 负责人: John Sayer
• 金额: $ 161.49万
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY007808%2F1
• 关键词: Rare; Disease; Research; Platform; renal

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.

一组罕见的遗传性肾脏疾病被称为肾纤毛病，约占所有肾衰竭患者的10%，这些患者需要接受包括透析和肾移植在内的专业治疗。现代遗传学和细胞生物学现在让我们对这类疾病有了一些重要的见解。最常见的形式被称为常染色体显性遗传性多囊肾病，最近第一批药物已经进入临床来减缓这种疾病。预防或关闭这种疾病的治疗方法仍然缺乏。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巨大的未得到满足的挑战。它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人。我们相信，通过调整这些患者队列，利用我们在分子诊断、深入临床表型和疾病建模方面的专业知识，我们可以加快新疗法的开发。在这里，我们将为对肾脏纤毛疾病感兴趣的临床医生和科学家创建一个可访问的多机构、多学科的协作网络。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高效的数据共享。通过将不同的肾脏纤毛病患者聚集在一个网络中，我们可以从我们的人类疾病遗传学中获得关于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细胞的功能分析，以了解疾病机制，并快速发现肾脏纤毛疾病急需的治疗药物。肾脏纤毛病国家网络(RCNN)的目标是：将临床、成像和分子遗传学工作作为英国所有肾脏纤毛病患者的标准工作；改进对潜在基因变异的基因组解释，并发展具有良好特征的患者群体，这些患者已准备好接受新的个性化药物治疗。在这样做的过程中，我们将通过与患者团体和慈善机构的伙伴关系，创建一个支持纤毛疾病患者及其家人的全国性系统，更好地与临床护理团队和研究人员对接，而不受邮政编码的影响。我们相信，随着我们的发展，让患者参与这些塑造肾脏纤毛疾病翻译版图的早期步骤将导致更好地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罕见疾病投资创建RCNN将有助于建立与全国护理团队的强大临床联系，促进行业和患者倡导团体之间的成功关系，以建立有意义的合作，并创造机会倡导重大行业投资，以加速肾脏纤毛疾病新疗法的开发。总而言之，RCNN的目标是在全国范围内改善肾脏纤毛疾病患者的护理，为已做好试验准备的分层患者队列开发基础设施，并与学术界和产业界建立合作伙伴关系，以加快开发急需的新疗法。

项目成果

Certain heterozygous variants in the kinase domain of the serine/threonine kinase NEK8 can cause an autosomal dominant form of polycystic kidney disease.

丝氨酸/苏氨酸激酶 NEK8 激酶结构域中的某些杂合变异可导致常染色体显性遗传形式的多囊肾病。

• DOI: 10.1016/j.kint.2023.07.021
• 发表时间: 2023
• 期刊: Kidney international
• 影响因子: 19.6
• 作者: Claus,LauraR;Chen,Chuan;Stallworth,Jennifer;Turner,JoshuaL;Slaats,GiselaG;Hawks,AlexandraL;Mabillard,Holly;Senum,SarahR;Srikanth,Sujata;Flanagan-Steet,Heather;Louie,RaymondJ;Silver,Josh;Lerner-Ellis,Jordan;Morel,Chantal;M
• 通讯作者: M

Copy number analysis from genome sequencing data of 11,754 rare disease parent-child trios: a model for identifying autosomal recessive human gene knockouts including a novel gene for autosomal recessive retinopathy

11,754 例罕见疾病亲子三人组的基因组测序数据的拷贝数分析：识别常染色体隐性人类基因敲除的模型，包括常染色体隐性视网膜病的新基因

• DOI: 10.1016/j.gimo.2024.101834
• 发表时间: 2024
• 期刊: Genetics in Medicine Open
• 作者: Olinger E

Allelic effects on uromodulin aggregates drive autosomal dominant tubulointerstitial kidney disease.

• DOI: 10.15252/emmm.202318242
• 发表时间: 2023-12-07
• 期刊: EMBO MOLECULAR MEDICINE
• 影响因子: 11.1
• 作者: Schiano, Guglielmo;Lake, Jennifer;Mariniello, Marta;Schaeffer, Celine;Harvent, Marianne;Rampoldi, Luca;Olinger, Eric;Devuyst, Olivier
• 通讯作者: Devuyst, Olivier

Many lessons still to learn about autosomal dominant polycystic kidney disease.

• DOI: 10.1007/s44162-023-00017-8
• 发表时间: 2023
• 期刊: Journal of rare diseases (Berlin, Germany)

Genetic analysis and outcomes of Omani children with steroid-resistant nephrotic syndrome.

• DOI: 10.1002/mgg3.2201
• 发表时间: 2023-09
• 期刊: Molecular genetics & genomic medicine
• 影响因子: 2