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

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.

Renal ciliopathies are a group of inherited cystic kidney diseases that represent around 10% of all patients with kidney failure. The most prevalent form worldwide is called autosomal dominant polycystic kidney disease (ADPKD) secondary to mutations in the cystogenes PKD1 and PKD2. Cystogenesis secondary to these mutations is driven by upregulated cAMP which can be modified in animal and human studies by arginine vasopressin antagonists such as tolvaptan. Pharmacological treatments and genetic interventions that prevent or switch off the disease are still lacking. Therapies for the related autosomal recessive (AR) disorders ARPKD and nephronophthisis is completely lacking despite shared disease mechanisms. Collectively these disorders are termed renal ciliopathies.
The objectives of the renal ciliopathies national network (RCNN) are 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 aim to create a national system of support for ciliopathy patients and their families through partnerships with patient groups and charities. This will allow better interfaces with clinical care teams and researchers. We believe that involving using the ADPKD translational pathway we can shape the translational landscape for all renal ciliopathies, leading to better mechanistic understandings, well designed preclinical and clinical trials and identifying therapies that would be used in these patient groups.