Challenge: Type 2 diabetes (T2D) affects 1 in 11 individuals worldwide and leads to severe complications such as diabetic nephropathy (DN) that is present in about 40% of T2D patients. DN progresses from subclinical disease (microalbuminuria) to overt nephropathy, end-stage renal disease requiring dialysis or transplantation. Identifying T2D patients at risk is problematic because even albuminuria does not always precede worsening renal function. Treating all patients when only about 40% will be affected is not feasible considering the cost and associated risks of such intervention. Solution: The team is developing predictive tools for susceptibility to diabetic nephropathy based on genetic markers present in T2D subjects before the occurrence of any renal defect. Their work builds on results obtained from a large trial on T2D where 1,110 patients were followed. The team has identified genes associated with renal impairment and is looking at variations of these genes that could be associated with the risk of developing renal complications. These genomic signatures can also be used to evaluate important co-morbidities and complications of T2D such as major macrovascular events, myocardial infarction, stroke and heart failure. Achievements/Impact: The algorithm (PRS: Polygenic Risk Score) developed by the researchers used 598 genetic variants encompassing the main risk factors of diabetes complications. The PRS is also adjusted for individualized geo-ethnicity, sex, age of onset of diabetes and diabetes duration. This new tool to predict susceptibility to diabetic nephropathy has a better predictive performance that the two clinical scores most used in clinical practice today. The PRS predicting albuminuria has already been validated in two independent cohorts, Clinpradia (T2D patients from mainly Celtic origin) and Post-Monica (pre-diabetic participants of Slavic origin) studies. The team has submitted a patent application to USPTO. OptiThera has already started discussion with two companies interested to license the PRS and to commercialize the technology as a service while improving it using artificial intelligence. Moreover, the success of this project allowed the team to obtain a second contribution from CQDM and Les Laboratoires Servier (France) to apply the PRS to patients from other ethnic origins (including Asian, Afro-American and Hispanic populations).
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Principal Investigator
Pavel Hamet Centre de recherche du CHUM, Université de Montréal Co-Investigator Ramzan Tahir Completed Project $ 683,665 / 2 years Supported by CQDM through: And by co-funding partner: |
