Proteomic approaches for novel systemic lupus erythematosus (SLE) drug discovery

ABSTRACT

Introduction: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a high risk of morbidity and mortality; however, there is no cure and the current medications are far from optimal in addressing efficacy and safety concerns. Over the past decade, various emerging technologies have been used in the search for novel drug targets of SLE which have resulted in numerous promising data. However, the systematic review and careful digestion of this information have been lacking.

Areas covered: In this review, the authors summarize promising biomarkers and drug targets which have been identified via various multiplexing and high-throughput proteomic strategies. The authors also introduce emerging technologies which are hopeful to be used for the discovery of novel biomarkers and therapeutic targets of SLE in the near future.

Expert opinion: Emerging proteomic technologies and genome-wide association studies (GWAS) have been the new driving forces in the discovery of novel biomarkers and promising therapeutic targets of SLE. Careful validation of these potential targets in lupus mouse models and clinical trials are urgently needed so that the next generation of target-specific medications can be developed for SLE patients.

KEYWORDS:

• Aptamer
• biomarker
• drug target
• lupus
• proteomics

Article highlights

• Two broad categories of conventional proteomic technologies, mass spectrometry (MS)-based technologies and multiplex high-throughput protein arrays, contribute to the discovery and validation of biomarkers and drug targets in SLE.

• Cell surface molecules in addition to cytosolic cytokines, chemokines, mediators, and enzymes, could serve as therapeutic targets in lupus.

• Further Clinical investigations are warranted for high potential target molecules from murine lupus studies.

• Emerging technologies CyTOF- and SOMAmer-based proteomics may provide more comprehensive screening and identification of valuable therapeutic targets in SLE.

• Aptamers are promising in drug target screening assays and the same aptamers may, in turn, serve as oligonucleotide drugs.

This box summarizes key points contained in the article.

Acknowledgments

We sincerely acknowledge Mr. Bailey Keyser for aiding in editing the manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This work was supported by the Lupus Research Alliance [grant number 376484].