MRC Human Genetics Unit
Medical Research Council Human Genetics Unit

Renal Ciliopathies National Network launches

The network, part of the £14 million MRC and NIHR funded UK Rare Disease National Platform, aims to improve the care of children and adults affected by renal ciliopathies: October 2023


CILIAREN - the Renal Ciliopathies National Network – was scientifically launched at the autumn meeting of the UK Cilia Network on Friday 6 October at the Institute of Genetics and Cancer. Its clinical launch will take place in Edinburgh during Kidney Week in May 2024.

Renal ciliopathies represent a group of inherited disorders characterised by cystic kidney disease, nephronophthisis, and syndromic ciliopathies. The underlying disease pathogenesis is related to abnormal structure or function of primary cilia- tiny hair-like organelles on the surface of our cells which function like antennae in sensing environmental or developmental signals.

This group of rare diseases, managed by healthcare professionals including nephrologists and geneticists, account for around 10% of all forms of kidney failure, affecting several thousand people across the UK.

As co-Director of the Node, Professor Pleasantine Mill and her research group will leverage their understanding of 'variant-to-function' to learn how genetic changes lead to cystic disease phenotypes in the kidney and liver.

Professor Mill will be collaborating with co-Directors across the UK - Professor John Sayer (Newcastle University), Professor Albert Ong (University of Sheffield), Tess Harris (Director, PKD Charity UK), and Professor Eamonn Sheridan (University of Leeds, Director Board of GeCIPs at Genomics England). The network will work closely with leading patient charities including PKD International, the Ciliopathy Alliance and BBS UK, as well as other academic and industrial stakeholders.

The vision of the Node is to develop a national network and framework to improve the identification, diagnosis and management of patients with renal ciliopathies, enhance the education and training of medical practitioners caring for patients, and to inform innovative new therapies.

Work at the Unit will involve a project to develop cell-based assays for renal ciliopathy patients for deep phenotyping: improving diagnosis, prognosis and understanding of genotype-phenotype relationships.

Crucially, this will allow the team to define disease-causing phenotypes in patient cells as the baseline needed to correct or revert from with therapeutic interventions.

The aim is to scale these up for high-throughput screening protocols using human urine-derived renal epithelial cells (URECs), which can be grown in 2 and 3-dimensions to study subsequent defects leading to cystogenesis. This phenotyping pipeline can be evolved into a valuable platform for drug testing and personalized medicine going forward.

Expertise and facilities in advanced imaging, bioinformatics and phenotyping at the Institute of Genetics and Cancer will contribute to this ambitious project.

The team will also be looking at genetic modifiers with the Sayer lab, running a pilot experiment to determine whether the phenotyping platform is sensitive enough to functionally test identified genetic variants associated with an atypical course of kidney disease onset or progression, as a means to improve prognosis for renal ciliopathies.

There is urgent need for accessible expert care and new therapies to prevent the need for dialysis and transplant for people living with renal ciliopathies. Our genomic and genetic approaches to molecularly characterise and deeply-phenotype patient cohorts offer exciting new opportunities to explore disease mechanisms and accelerate development of therapeutic interventions.

Pleasantine Mill, Professor of Cilia BiologyMRC Human Genetics Unit  

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