The pharmaceutical industry is facing significant challenges, including rising costs and escalating demands from regulatory authorities to develop a more precision-medicine-based approach to drug development.
Olink’s PEA technology is seeing more widespread use in the identification of new drug targets and analysis of clinical trial samples. This analysis involves stratifying patient populations, predicting responses, and providing key insights into drug modes of action and disease biology.
This article summarizes some recent studies that illustrate the central role of protein biomarker research in therapy discovery and development.
Multiomic profiling of atherosclerotic instability
Atherosclerotic cardiovascular disease (ASCVD) continues to be a significant global health issue that is linked to a high degree of morbidity and mortality from ischemic stroke (IS) and myocardial infarction (MI).
Patients with unstable, symptomatic ASCVD face a more than 10-fold higher annual risk of stroke than those with stable, asymptomatic disease.
Scientists from Novo Nordisk A/S in Denmark and the Karolinska Institute in Stockholm have undertaken an innovative study of carotid stenosis patients. This study integrates multiomic data acquired locally from atherosclerotic plaques and from the peripheral circulation.
The researchers combined metabolomics, transcriptomics, and proteomics measured using five Olink® Target 96 panels, employing the Data Integration Analysis for Biomarker discovery using Latent cOmponents (DIABLO) machine learning method. This method derived molecular signatures associated with CVD outcomes, atherosclerotic plaque stability, and therapeutic responses.
Using proteomics, it was possible to identify a total of 15 proteins closely linked to atherosclerotic disease symptomatology. These proteins overlapped in plasma taken from locations adjacent to plaque lesions and from the peripheral circulation.
Both well-established atherosclerosis markers and more novel proteins were identified, including PCOLCE, FUT5, ICOSLG, CCL20, CA6, and KITLG.
It was observed that cytokine-receptor interaction pathways and chemokine signaling were upregulated in both sample types, while the IL-17 pathway was enriched only locally.
Integrated multiomics enabled the identification of distinct symptomatology-associated profiles of metabolites, transcripts, and proteins that differed when analyzed peripherally. These were found at either the disease site or at the intersection of these compartments.
It was noted that:
- FABP4, IL6, Sphingomyelin, and Bilirubin were the most prominent analytes in the periphery.
- F11, ANGPTL3, ITGB1, ICOSLG, and Sphingomyelin were the most prominent analytes locally.
- FABP4, C1R, IL6, Sphingomyelin, and Bilirubin were prominent at the intersection.
- Pathway analysis showed that necroptosis, inflammation, coagulation, and cholesterol metabolism were key determinants of symptomatology.
Higher peripheral plasma protein levels of ANGPTL3 were also determined to be closely linked to more frequent significant adverse cardiac events and all-cause mortality.
It was noted that the testing of prioritized targets from the multiomic analysis against the public OpenTargets platform showed good evidence for the genetic involvement of F11, EGFR, IL6, C1S, and ANGPTL3 in cardiovascular diseases.
A 2026 study summarized the impact of this work:
The targets presented here could have paradigm-shifting implications, especially for enabling tailored therapies and precision medicine in the fight against carotid atherosclerosis.
Das et al. 2026
A novel proteomics approach to identify immunomodulatory drugs for psychiatric conditions
Major depressive disorder (MDD) is a widespread neuropsychiatric disorder impacting more than 250 million people globally. It represents a significant healthcare and economic resource burden.
There is evidence to suggest that a subset of MDD patients exhibit a dysregulated immune system, in turn suggesting pathophysiological overlaps with apparently unrelated diseases.
Researchers from the Icahn School of Medicine at Mount Sinai, NY, investigated whether MDD patients’ proteomic profiles are similar to the profiles of patients with the inflammatory skin diseases psoriasis (PS) and atopic dermatitis (AD).
Targeted immunomodulatory drugs have revolutionized the treatment of PS and AD in recent years.
The team employed multiple Olink® Target 96 panels to look for overlapping dysregulated proteins among MDD, PS, and AD patients. A computational approach was used to explore repurposing opportunities to treat MDD with existing drugs approved for PS or AD therapy.
All three of these diseases feature distinct protein profiles, but a set of proteins was dysregulated in all three patient groups, including TNFSF14 (T-cell markers); CCL13, CCl17 (Th2 cytokines); CXCL9, CXCL10, CXCL11 (Th1 cytokines); and CD40LG. Across the three diseases, pathway analysis confirmed shared enrichment indicative of Th2 up-regulation.
The anti-IL-4Rα monoclonal antibody dupilumab is commonly used to treat AD, and the researchers identified a potential opportunity to repurpose it through in silico druggability analysis of these shared proteins.
Published data from clinical trials using dupilumab to treat AD showed that a number of the Th2 proteins shared between MDD and AD were influenced by the drug.
A mouse model of psychosocial stress also revealed that inhibition of IL-4Rα lowered stress-induced behaviors in these animals.
The back-translational drug repurposing strategy employed in this study may offer a novel approach to identify immunomodulatory drugs in psychiatry.
He et al. 2026
Biomarker insights from a clinical trial for mRNA CAR-T cell therapy for myasthenia gravis
Chimeric antigen receptor (CAR)-T cell therapies have the potential to reset the immune system, revolutionizing the treatment of autoimmune disease. Adoption has been limited, however, with issues such as the risk of cytokine release syndrome, the need for inpatient therapy, and non-specific immunosuppression slowing its uptake.
RNA-based cell therapy could overcome some of these key limitations. A team from Cartesian Therapeutics (MA, USA) employed the Olink® Target 96 Inflammation panel to monitor cytokine responses in patients with generalized myasthenia gravis (MG) participating in a phase 2b clinical trial.
The monitored patients were given Descartes-08, an autologous, RNA-encoded anti-B cell maturation antigen (BCMA) CAR-T cell therapy. It was observed that administering Descartes-08 in an outpatient setting led to durable clinical efficacy.
Multiomic analysis revealed a precision retuning of self-reactivity demonstrated by a combination of reduced activity of BCMA+ plasma cells and plasmacytoid dendritic cells, as well as increased pro-immune function.
Olink analysis confirmed that the administration of Descartes-08 was not associated with protein changes indicative of unwanted CAR-T cell therapy-induced inflammation.
After three months, a positive effect on decreasing multiple markers associated with autoimmunity was observed, most notably reductions in IL-6, IL-24, CCL19, and ARTN.
It was also noted that a number of other proteins relevant to autoimmune inflammation and immune reset decreased by month 12, including TRAIL, EN-RAGE, and TNFSF14. TGF-β1 was also reduced at 12 months. This is involved in immune reset after CAR-T cell therapy.
The specific changes in immune signatures without broad suppression support a precision immune reset that results in durable clinical improvement.
Fedak et al. 2026
A custom biomarker panel defines CKD-associated protein responses in T2D patients treated with dulaglutide
Chronic kidney disease (CKD) represents a significant complication of type 2 diabetes (T2D), impacting between 20 % and 50 % of patients worldwide. Drugs like glucagon-like peptide-1 receptor agonists (GLP-1RAs) offer significant benefits in this respect.
Scientists from Eli Lilly in Indianapolis, IN, and the Joslin Diabetes Center in Boston, MA, undertook a post hoc proteomic analysis of the AWARD-7 clinical trial for dulaglutide (Dula), a long-acting GLP-1RA drug.
Previous biomarker discovery studies identified a total of 64 circulating proteins that were closely linked to elevated risk of end-stage kidney disease (ESKD) in people with diabetes.
A 21-protein Olink® Flex panel was designed from these proteins. This panel was referred to as the Joslin Kidney Panel (JKP) and included key ESKD-associated markers, including ligands, inhibitors, immunoregulatory receptors, TNF receptors, and other receptors.
This panel measured longitudinal changes in the trial participants’ plasma levels treated with either Dula or the insulin analog glargine.
It was observed that 14 JKP markers increased over a six-month period in patients on glargine, while these markers decreased in Dula-treated individuals with statistically significant between-group differences. The most notable differences were observed in eight TNF receptors and in mediators of apoptosis and inflammation.
The stratification of patients by key clinical variables at baseline highlighted the differential effects of Dula based on these characteristics. Measurement via estimated glomerular filtration rate (eGFR) revealed that Dula’s effects on circulating JKP proteins were three times larger in patients with severe versus moderate kidney dysfunction.
Variations in JKP protein responses to Dula were also observed when stratifying by other key clinical factors, for example, HbA1c, BMI, or UARC.
These novel observations suggest that the effect of Dula is conditional on levels of baseline clinical variables. Thus, physicians can identify individuals who, in the long term, may benefit the most from Dula treatment regarding reduction in risk of kidney outcome by examining the six-month decline in concentration of JKP proteins in circulation according to the baseline levels of clinical variables.
McFarlin et al. 2026
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