Marie Curie Industry-Academia Pathways and Partnerships (IAPP)

 

The number of patients with chronic kidney disease (CKD) is increasing steadily due to extended life expectancy, long lasting diabetes and obesity. Several therapeutic strategies exist for the treatment of chronic kidney diseases, most involving either interference (inhibition) of the renin/angiotensin system and/or anti-inflammatory agents. While these therapeutic approaches have shown clear benefits for the patients, their potential impact is compromised by late administration at a quite advanced state of disease, due to a lack of sensitive and specific methods for the early detection of disease. Unfortunately, while therapy at an early stage has been reported to be curative, therapy at late stages can only delay disease progression, highlighting the clear need for early detection. Early unambiguous detection of patients at risk is both a clinical and scientific challenge. However, given the enormous burden on health care systems, this challenge has to be met.

Urinary proteomic biomarkers can provide clinical information for the early detection and differential diagnosis of diseases while avoiding invasive procedures, indicating a clear need for the identification of urinary proteomic biomarkers of chronic kidney disease, generalization of their use and their implementation into a high throughput screening tool. These are the long term scientific objectives of this Marie-Curie exchange program, which -as described in detail in the workpackages- will be easier reached following the knowledge transfer and coordination of the activities of the participating parties.

Due to the complexity of the disease, single biomarkers will likely not enable assessment wit high specificity and sensitivity, hence a multi-parametric approach has to be employed. Among those, mass spectrometry, and especially capillary electrophoresis coupled to mass spectrometry (CE-MS) has been shown to represent an excellent tool for the discovery and validation of urinary biomarkers of CKD. These biomarkers, when combined to a panel, enable diagnosis, but also prognosis of disease progression and assessment of therapeutic strategies. The aim of this projectis 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.

Major methodological goals of this project are:

  • Development of normalization software to establish CEMS portability
  • investigation of the correlations of CE- and MALDI- MS data and development of mathematical tools for their automated adjustment and matching,
  • development of efficient MALDI assays for the detection of CKD biomarkers
  • evaluation of the efficiency of the MALDI assays in a limited number of clinical samples,
  • establishment of respective databases for MALDI data recording,
  • establishment of appropriate software for MALDI data quantification and normalization,
  • correlation of MALDI MS to CE-MS biomarker relative quantification data.

It should be noted that even though during the course of this proposal the platform will be optimized for the detection of specific CKD markers, it is expected that many of the tools generated during this process will be generic with potential to be employed in addressing additional clinical objectives. Further validation of the optimized set-up according to ISO 13485 guidelines and its development to an inexpensive assay for implementation into clinical routine is anticipated through further collaborative studies between the partners in the future.

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.