GlySign aims at the implementation of known glycomic markers for Precision Medicine into clinics by exploiting the key translational synergies between excellent academic and non‐academic partners.
Glycosylation is one of the most complex and prevalent posttranslational modifications of proteins; it is the process of enzymatic attachment of glycans, i.e. complex sugars. The name GlySign refers to the distinctive and complex changes in the glycomics profiles – or Glycan Signatures – of the body’s glycoproteins that occur during progression of many chronic diseases. Targeting the level of technology development and marker validation in the innovation chain, we will address a current unmet need in the market by establishing a new in vitro diagnostic platform for the clinical exploitation of glycomic biomarkers for Precision Medicine (also known as ‘Personalized Medicine’).
To this end, GlySign research will be focused on medical glycomics applied to four model diseases in which specific changes in the glycosylation patterns of blood glycoproteins are known to occur and are candidates for glycomics based assays for Precision Medicine:
Diabetes: Up to 8% of European diabetes patients are estimated to have MODY (Maturity Onset Diabetes of the Young) – but often they are incorrectly diagnosed as having either Type 1 or Type 2 diabetes, which results in ineffective, sometimes detrimental, medical treatment. The GlySign partner Genos showed for the first time that distinct changes occur in the antennary fucosylation of plasma proteins in MODY patients . This phenomenon will be exploited within GlySign by developing a glycomics-based clinical diagnostic assay for stratification of diabetes patients. (Elham Memarian and Daniel Demus)
Prostate cancer: The concentration of prostate-specific antigen (PSA) is worldwide used as an early screening marker for prostate cancer. Unfortunately, this PSA-test is unable to provide the desired predictive value, high sensitivity and specificity that is needed to distinguish indolent from malignant prostate cancer. Therefore, recent studies have investigated if specific glycomic features of PSA could provide a better insight in differentiating aggressive from non-aggressive prostate cancer, avoiding unnecessary biopsies and overdiagnosis . Within GlySign, PSA glycomics assays will be developed to study glycomic alterations in prostate cancer progression in patients. (Alan Moran)
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the main cause of severe thrombocytopenia in newborns (which leads to severe complications and long-term disabilities). Immunoglobulin G (IgG) glycosylation features were shown to be a key marker in predicting FNAIT pathology . In GlySign, glycomics-based Precision Medicine assays will be established to assess FNAIT severity. (Iwona Wójcik)
Rheumatoid arthritis (RA): The Fc glycosylation of serum IgG is known to change in RA patients, being particularly pronounced in autoantibodies even at an early disease stage . GlySign will study plasma IgG glycosylation from patients at various stages of RA progression, using a range of orthogonal glycomics methods from highly detailed LC-MS profiling of fluorescently tagged Fc N-glycans to high-throughput quantitative microplate assays of specific glycan parameters in whole IgG glycoprotein. These represent the two ends of the spectrum of glycomics methods employed in translation of glycomics analyses from research tools to clinical grade Precision Medicine assays. (Thomas Sénard and Osmond Rebello)
Throughout the training programme we will reinforce a robust model of Precision Medicine being developed by LUMC, Ludger and Genos that involves a multi-staged approach to patient stratification and diagnostics. In this, we promote the idea that glycomics-based clinical assays (a) must only be used if they add significant diagnostic or prognostic value, (b) must be economically viable and (c) must be appropriately integrated with other tests in the diagnostic pathways.
 Lauc et al. PLoS Genet. 2010 Dec 23;6(12):e1001256. doi: 10.1371/journal.pgen.1001256
 Yoneyama et al., Biochem Biophys Res Commun. 2014 Jun 13;448(4):390-6. doi: 10.1016/j.bbrc.2014.04.107
 Kapur et al., Blood, 20162014, 123(4):471-480. doi: 10.1182/blood-2013-09-527978; PMID: 24243971
 Rombouts et al., Ann Rheum Dis, 2015, 74(1):234-241. doi: 10.1136/annrheumdis-2013-203565. PMID: 24106048