CY-BioMUC1

Autosomal Dominant Tubulointerstitial Kidney Disease due to MUC1 mutations in Cyprus – Preparation of a clinical trial cohort, biomarker discovery and identification of new MUC1 mutations

This 2-year long project is designed to study clinical and molecular aspects in Cypriot patients with Autosomal Dominant Tubolointerstitial Kidney Disease due to mutations in MUC1 (ADTKD-MUC1). The general objectives of this project are:

1. To establish a clinical trial cohort to test a repurposed drug as a candidate treatment for ADTKD-MUC1
2. To identify diagnostic and prognostic biomarkers that will facilitate confident monitoring of the progress of patients and their response to the candidate treatment
3. Update and enrich the existing registry of ADTKD-MUC1 patients of the Molecular Medicine Research Center (MMRC) and identify new mutations in MUC1 or other ADTKD related genes explaining the Tubulointerstitial Nephropathy (TIN) observed in patients genotyped negative for the common mutation in MUC1.

ADTKD-MUC1 – previously known as Medullary Cystic Kidney Disease type 1 (MCKD1), also reported as MUC1 Kidney Disease (MKD) – is a rare TIN that leads mutation carriers to end-stage renal disease (ESRD). It is remarkable that on a world-wide scale the highest number of patients suffering by this disease have been described in Cyprus, with the region of Paphos being the epicentre where the recurrence of this mutation is spotted the most.  This project aims to deeply characterize the phenotype of ADTKD-MUC1 patients in Cyprus, discover progression biomarkers and in extent detect the most informative indicators to monitor the response of patients to a therapeutic intervention. It is quite important for both ADTKD-MUC1 patients and the scientific community in Cyprus to organize and execute the first drug trial of this kind and treat a monogenic chronic kidney disease.

The existence of large families with ADTKD-MUC1 in Pafos had assisted our group in 1998 to be the first to identify the critical region in chromosome 1q21.1 in search of the mutation causing the disease. This mutation had been elusive for several years and was discovered in 2013 by a group at the Broad Institute of MIT and Harvard. In the scope of a prospective clinical trial and deep study of the disease, we joined forces with the ADTKD-MUC1 Consortium, led by the Broad Institute. This project aims to complement a much wider effort coordinated by the Broad Institute, with the main objective to find a cure for patients with ADTKD-MUC1.