Key Strengths and Technologies

Key Strengths and Technologies

1. Clinical and clinic-pathological cohorts, 2. iPS cell technology, 3. High throughput miRNA screening, 4. Lipidomics, 5. Computational approaches to ‘personalized’ medicine, 6. Proof-of-concept Cluster, 7. Translational Cluster and direct pathway to commercialization.

[1] Clinical and clinic-pathological cohorts

RiskyCAD has access to unique CAD patient cohorts essential for new biomarker discovery. The Cosortium’s initial findings and leads on biomarker candidates are based on large scale analysis of the LURIC study. The LURIC database contains currently over 2000 potential biomarker entries per individual. In addition, the full cohort has been genotyped with the Affymetrix 6.0 chip technology and Zora Biosciences has screened with various lipidomic platforms selected groups of patients with carefully phenotyped CAD manifestations. These initial studies have resulted in emerging lipid biomarkers with high sensitivity and specificity (both >75%) for identification of vulnerable CAD patients. Other carefully selected cohorts include the COROGENE study from Finland and the SPUM-ACS study from Switzerland. The ILLUMINATE trial samples may also be used to test and validate our novel biomarkers and risk assessment models in a clinical trial setting.

[2] iPS cell technology

The induced pluripotent stem (iPS) cell technology offers new opportunities to drug discovery. Induced pluripotent stem (iPS) cells can be obtained from any individual and can be differentiated into various cell types, thus allowing the investigation of disease pathogenesis in relevant genotype and disease specific human models. UTA has expertise in derivation of patient-specific iPSCs. In RiskyCAD, it will focus on the generation of hepatocyte models from patient cohorts with angiographically verified stable coronary artery disease w/o acute events, and cohorts with plaque rupture and acute coronary event. UZH will in turn work on the generation of vascular cells such as endothelial and smooth muscle cells. The disease specific cell models will be subjected to lipidomics and miRNA analysis complemented with genotypic and functional analyses.

[3] High throughput miRNA screening

CBC (previously Febit GmbH) possesses state-of-the-art microarray and next generation sequencing platforms for whole transcriptome biomarker discovery. In RiskyCAD, these will be used to identify and validate microRNA biomarkers for the non-invasive assessment of CAD risk. Subsequently, an IVD-certified qRT-PCR platform that ensures conformity to regulatory bodies will be developed.

[4] Lipidomics

Lipidomics based on modern mass spectrometer technologies enable the very sensitive detection (attomolar level or less) and absolute quantification of molecular lipids in biological tissues or fluids. Leading lipidomics company, ZORA has the broadest and most thorough lipidomics platform currently available, and has already applied it successfully to identify emerging lipid biomarkers in serum/plasma from patients with CAD. In RiskyCAD, Zora Bioscience will apply its platform more extensively, in distinct biobanks, towards the validation of risk prediction potential of molecular lipids and the development of a new diagnostic kit limited to only a couple of key molecules.

[5] Computational approaches to ‘personalized’ medicine

RiskyCAD employs powerful computational tools for ‘personalized’ medicine. BIOVISTA applies state-of-the-art predictive modelling and link identification capabilities (such as the COSS platform) to exploit unique genetic, biochemical and clinical characteristics of a patient with the aim to identify novel biomarkers or reposition existing ones from related diseases, and select the drugs or drug combinations that will best match the patient’s profile. BIOVISTA’s approach is supported by one of the world's largest databases with over 4 billion biological correlations that exploits seemingly disparate biological correlations to deliver novel insights and recommendations of immediately applicability. Additional adverse event profiling analysis and drug repositioning programs, further help fulfil patient stratification and develop new diagnostic and therapeutic approaches in a translational ‘personalized’ medicine context.

[6] Proof-of-concept Cluster

To support the strong translational focus of the Consortium, a cluster of groups of unique skills and complementarity has been assembled. This comprises pioneering teams in relevant human and mouse disease models and methodologies for proof-of-concept studies (BRFAA, UMIL, UOXF). Of particular importance are innovative carrier technologies that enhance effective delivery of oligonucleotide-based therapeutics (siRNA, miRNA and antisense DNA molecules) into the liver and atherosclerotic plaques.

[7] Translational Cluster and direct pathway to commercialization

RiskyCAD is an SME-oriented proposal. Four pioneering SMEs and one large entreprise (potential end-user) are working in close collaboration with clinicians and basic researchers to achieve the proposal’s objectives. ZORA and CBC apply unique best-in-class analytical platforms for phenotype characterization, discovery of translational biomarkers, and identification of disease pathways and targets. BIOVISTA applies unique predictive modeling platforms to identify novel biomarkers and ‘repurpose’ drugs to new indications. GENOWAY consults clients and develops preclinical animal models of disease. Most importantly, SYNLAB, one of the largest and more rapidly growing clinical laboratory service providers in Europe introducing on average 60 new diagnostic methods per year, will evaluate new biomarkers originating from RiskyCAD, perform market research through its established network of clients and develop commercial applications, thus ensuring immediate translation of discoveries into medical practice.