Emerging Peptide Therapeutics for Inflammatory Autoimmune Diseases

Abstract

Current pharmacologic treatments for inflammatory diseases are largely palliative rather than curative. Most of them result in nonspecific immunosuppression. This can be associated with disruption of natural and induced immunity with significant, sometimes dramatic, adverse effects. Among the novel strategies that are under development, tools that target specific molecular pathways and cells, and more precisely modulate the immune system to restore normal tolerance mechanisms are central. In these approaches, peptide therapeutics constitute a valuable class of therapeutic agents. They possess a number of intrinsic properties that are favorable for long-term treatments. They are also versatile components that can be modified to improve their capacities without affecting their bioactivity. Peptide-mediated immunotherapy has been evaluated in several appropriate experimental animal models. A few peptides are currently evaluated in clinical trials for the treatment of human chronic inflammatory diseases. In this review we describe a number of these emerging peptide therapeutics. We also discuss future challenges that, in addition to include selection of appropriate peptide drugs, also involve the optimization of peptide dosage and route of administration as well as the improvement of peptide stability for adequate bioavailability and specific targeting.

Nucleic acid-associated autoantigens: Pathogenic involvement and therapeutic potential

“…Despite promising results in mouse models, antigen-specific immunotherapy has not yet been very successful. A few on-going clinical trials only hold promise and might represent future roads for immunotherapy in autoimmune diseases [330].…”

“…Peptide analogues and notably altered peptide ligands that have the capacity to deviate the signal transduction events following their interaction with the T cell-receptor were designed, and some of them were found to partially restore the normal immune response in mouse models (for a recent review see [330]). Promising results were obtained with ATX-MS-1467, a preparation made of a mixture of four soluble MBP peptides tested in an open phase I/IIa clinical trial involving patients with MS (Apitope Technology Ltd, Bristol, UK).…”

Nanomaterials, Autophagy, and Lupus Disease

“…We and others recently reviewed the numerous advantages of peptide‐based approaches in treating lupus and other autoimmune diseases . There is a notable increased interest in peptides over other types of drug candidates such as therapeutic fusion proteins or monoclonal antibodies .…”

“…There are, however, various ways to circumvent these liabilities, by modifying either side chain residues or the polypeptide backbone. Such changes can efficiently minimize some of the intrinsic difficulties of peptides …”

Advances in the Prediction of Protein–Peptide Binding Affinities: Implications for Peptide‐Based Drug Discovery

“…Recently, there have been exciting developments in peptide science, and commercial interest in peptides is growing, especially as novel pharmaceutical agents (1)(2)(3). Computational methods, like docking and virtual screening, can be used to facilitate peptide drug discovery (4).…”