Therapeutic peptides for the treatment of systemic lupus erythematosus: a place in therapy

ABSTRACT

Introduction

Studies in vitro and in vivo have identified several peptides that are potentially useful in treating systemic lupus erythematosus (SLE). The rationale for their use lies in the cost-effective production, high potency, target selectivity, low toxicity, and a peculiar mechanism of action that is mainly based on the induction of immune tolerance. Three therapeutic peptides have entered clinical development, but they have yielded disappointing results. However, some subsets of patients, such as those with the positivity of anti-dsDNA antibodies, appear more likely to respond to these medications.

Areas covered

This review evaluates the potential use of therapeutic peptides for SLE and gives an opinion on how they may offer advantages for SLE treatment.

Expert opinion

Given their acceptable safety profile, therapeutic peptides could be added to agents traditionally used to treat SLE and this may offer a synergistic and drug-sparing effect, especially in selected patient populations. Moreover, they could temporarily be utilized to manage SLE flares, or be administered as a vaccine in subjects at risk. Efforts to ameliorate bioavailability, increase the half-life and prevent immunogenicity are ongoing. The formulation of hybrid compounds, like peptibodies or peptidomimetic small molecules, is expected to yield renewed treatments with a better pharmacologic profile and increased efficacy.

KEYWORDS:

• Pathogenesis
• systemic lupus erythematosus
• therapeutic peptides
• treatment
• peptibodies
• peptides

Article highlights

• Unlike other rheumatic diseases, the therapeutic armamentarium for SLE has been poorly impacted by the advent of biological agents and small molecules; hence, treatment mainly relies on the combination of traditional approaches which includes corticosteroids, antimalarials, disease-modifying anti-rheumatic drugs and immunosuppressive agents.

• The potential use of therapeutic peptides in SLE is justified by their cost-effective production, target selectivity, low rate of adverse events, and an overall immunomodulatory effect.

• Although no therapeutic peptide has been licensed for SLE treatment, the 21-mer peptide P140, the CDR1-based peptide and AMG623 have entered phase II or III clinical trials; they show a good safety profile but have mostly failed to achieve the primary endpoints despite positive results observed in some subsets of SLE patients.

• Preliminary findings regarding other peptides (pConsensus, laminin-derived peptide, nucleosomal peptides, DWEYS peptide, glatiramer acetate, and thymopentin-5) are encouraging; they show amelioration of glomerulonephritis, reduction in autoantibody titres, prevention of neuronal damage and an overall prolonged survival of SLE animal models.

• A better understanding of SLE pathogenesis and the improvement in biotechnologies should increase the number of peptides that can specifically neutralize a pathogenic pathway thus allowing a more personalized treatment.

• Because of their acceptable safety profile, therapeutic peptides could be added to standard of care of specific subsets of SLE patients potentially resulting in a sparing effect on immunosuppressants and glucocorticoids.

This box summarizes the key points contained in the article.

Author contributions

RT performed the bibliographic research and analysis, wrote the first draft of the manuscript, drew the figures, and critically implemented and revised the manuscript. MJL and FA critically revised the manuscript. All the authors read and approved the final version of 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.