PROTOCLIN

IMPROVEMENT OF TOOLS AND PORTABILITY OF MASS SPECTROMETRY-BASED CLINICAL PROTEOMICS AS APPLIED TO CHRONIC KIDNEY DISEASE

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 Obiettivo del progetto (Objective)

'The number of patients with chronic kidney disease (CKD) is increasing steadily due to extended life expectancy, long lasting diabetes and obesity. Early unambiguous detection of patients at risk is both a clinical and scientific challenge. Capillary electrophoresis coupled to mass spectrometry (CE-MS), developed by Mosaiques Diagnostics (MD, SME, Germany), has been shown to be an excellent tool for the discovery and validation of urinary biomarkers of CKD. The aim of this project is to advance CE-MS technology in biomarker discovery and direct clinical applications alike through a) establishing the appropriate tools for its portability and b) through its combination with MALDI TOF MS, as a pre-CE-MS high throughput screening tool, in the form of an integrated MS diagnostic platform. Participating partners are highly complementary: the research intensive participating SME (MD) being the inventor of and expert on CE-MS, BRFAA bringing expertise on MALDI TOF MS profiling and Inserm having extensively collaborated with MD and recently acquired CE-MS being an excellent b-site for the development of tools for CE-MS portability. The exchange and recruitment program has been designed so as to allow flow of scientific knowledge between industry and academia and training of early to late stage researchers in cutting edge biomarker discovery techniques. Multiple immediate and long term benefits for all participating parties are expected including higher efficiency in their current and expansion of their research activities and increase in competitiveness. Among the long term benefits will be the durable implementation of the CE-MS technology and the development of a non-invasive high-throughput screening tool for CKD.'

Introduzione (Teaser)

Chronic kidney disease (CKD) is a progressive loss in renal function over a period of months or years. The early detection of those at risk of developing CKD is necessary as the number of patients is increasing steadily worldwide.

Descrizione progetto (Article)

CKD results in renal failure and the mandatory requirement of renal replacement therapy, transplantation or lifelong dialysis. Several therapeutic strategies exist for treating CKD, with the majority involving either inhibition of the renin/angiotensin system or anti-inflammatory agents. While therapy at an early stage may be curative, therapy at late stages can only delay disease progression, highlighting the clear need for early detection.

The aim of the EU-funded PROTOCLIN project was to advance capillary electrophoresis coupled to mass spectrometry (CE-MS) technology in CKD biomarker discovery.

To achieve portability, a CE-MS platform was established in a partner laboratory. As this multidimensional approach mandates comparability of data sets, software solutions enabling the exchange and comparison of data from different instruments were developed. First validation assays confirmed portability and accuracy of both the platform and software. To reach this goal, PROTOCLIN initiated an intensive exchange of scientists between industrial and academic partners.

Project members demonstrated that urinary proteomic biomarkers can provide clinical information for the early detection and differential diagnosis of CKD while avoiding invasive procedures. This highlights a clear potential benefit for the application of urinary proteomic biomarkers of CKD, generalisation of their use and their implementation into a high-throughput screening tool.