Proteomics opens the door to many possibilities with regards to gaining a deeper understanding about the human body that could help patients and streamline medical care. For instance, analyzing protein expression patterns for diseases or ailments can reveal the biological pathways at play and find probable drug targets. If a Food and Drug Administration (FDA) approved drug exists for that drug target, the drug may prove beneficial in the treatment of the diseases or ailments.
A wonderful example of using proteomics to identify new applications for a drug and new drug targets was recently published in the Journal of the American Heart Association (JAHA). George et al. sought to determine if tocilizumab (a drug targeting interleukin 6 (IL-6)) may benefit people with cardiovascular problems (George et al., 2020). In earlier work, the team noted that IL-6 (known to fuel the inflammation process and contribute to autoimmune disorders) may play some part in coronary artery disease (CAD). They also reported that IL-6 levels are high before and after a heart attack and correlated with heart damage or death. For those with CAD, elevated levels of IL-6 can be indicative of early death. Therefore, tocilizumab and other drugs that target IL-6 may indeed benefit those with CAD.
Tocilizumab is FDA approved for the treatment of rheumatoid arthritis and other autoimmune disorders. In the first study of its kind, the team tested the drug in patients with non-ST segment elevation myocardial infarction (NSTEMI) – a less damaging form of a heart attack – patients about to have coronary angiography and compared the results to a placebo group. The team saw a reduction of C-reactive protein and troponin T (high levels of these proteins can signal increased risk of death (deFilippi et al., 2003)), great indications that the medication is proving beneficial in reducing damage to the heart.
Using our technology to compare the blood samples from the two groups, the team sought to determine the molecular underpinnings of the drug’s benefit. They found 11 proteins that changed in concentration with the administration of the drug, which include: IL- 6 receptor subunit alpha, alpha1- antichymotrypsin complex/serpin family A member 3 (SerpinA3), hepcidin antimicrobial peptide (HAMP), insulin- like growth factor- binding protein 4 (IGFBP4), myeloblastin/proteinase 3 (PRTN3), vascular endothelial growth factor A (VEGFA), IL- 6, Ck- beta- 8- 1, C- C motif chemokine ligand 23 (CCL23), complement component C5a anaphylatoxin (C5A) and lipopolysaccharide- binding protein (LBP). The team did do their due diligence and confirmed 8 out of 11 proteins with immunoassays.
From their research, the team hypothesizes that CCL23, PRTN3, LPB, HAMP and IGFBP4 play a crucial role in the benefits of tocilizumab. Perhaps, these proteins could become new drug targets. The research team does mention that more work is needed. However, it is thrilling that potential new ways that are already FDA approved for other conditions could help.
deFilippi, C., Wasserman, S., Rosanio, S., Tiblier, E., Sperger, H., Tocchi, M., . . . Henrich, W. (2003). Cardiac troponin T and C-reactive protein for predicting prognosis, coronary atherosclerosis, and cardiomyopathy in patients undergoing long-term hemodialysis. JAMA, 290(3), 353-359. doi:10.1001/jama.290.3.353
George, M. J., Kleveland, O., Garcia-Hernandez, J., Palmen, J., Lovering, R., Wiseth, R., . . . Ueland, T. (2020). Novel Insights Into the Effects of Interleukin 6 Antagonism in Non-ST-Segment-Elevation Myocardial Infarction Employing the SOMAscan Proteomics Platform. J Am Heart Assoc, e015628. doi:10.1161/JAHA.119.015628