GlySign aims to bring known glycomic clinical markers to the clinic for Precision Medicine (also known as ‘Personalized Medicine’) by exploiting the key translational synergies between excellent academic and non‐academic partners.

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 (PM).

glysign_innovation_chainTo this end, we will focus the training 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 Personalized 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 were the first to show through a series of studies that distinct changes occur in the antennary fucosylation of plasma proteins in MODY patients.[1] This phenomenon will be exploited within GlySign by developing a glycomics-based clinical diagnostic assay for stratification of MODY patients.

Prostate cancer: Recent studies have shown that glycosylation of prostate-specific antigen (PSA) has a great potential for improved sensitivity and specificity for diagnosis of prostate cancer patients[2]. Within GlySign, glycomics-based PM assays for longitudinal assessment of prostate cancer progression in susceptible patients will be developed.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the main cause of severe thrombocytopenia in newborns (which leads to severe complications and long-term disabilities). IgG glycosylation features have been shown to be a key marker in predicting pathology of FNAIT[3]. In GlySign, glycomics based PM assays will be established to assess foetal and neonatal FNAIT severity from maternal and neonatal blood and serum IgG.

Rheumatoid arthritis (RA): The Fc glycosylation of serum IgG is known to change in specific ways in patients with RA, being particularly pronounced in autoantibodies[4]. GlySign will study serum 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 PM assays.

Throughout the training programme we will reinforce a robust model of PM 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.

[1] Rombouts et al., Ann Rheum Dis, 2015, 74(1):234-241. doi: 10.1136/annrheumdis-2013-203565. PMID: 24106048

[1] Lauc et al. PLoS Genet. 2010 Dec 23;6(12):e1001256. doi: 10.1371/journal.pgen.1001256

[2] Yoneyama et al., Biochem Biophys Res Commun. 2014 Jun 13;448(4):390-6. doi: 10.1016/j.bbrc.2014.04.107

[3] Kapur et al., Blood, 20162014, 123(4):471-480. doi: 10.1182/blood-2013-09-527978; PMID: 24243971

[4] Rombouts et al., Ann Rheum Dis, 2015, 74(1):234-241. doi: 10.1136/annrheumdis-2013-203565. PMID: 24106048