Peptide-based Inhibitor for Treating Chronic Viral and Autoimmune Inflammatory Diseases
A novel peptide-based inhibitor of Rig-I-like receptor (RLR)-mediated signal transduction for therapeutic modulation of the immune response
Background
Rig-I-like receptors (RLRs) have emerged as critical sentinels of viral infection, surveying the cytosol of all mammalian cell types for the presence of viruses containing RNA genomes. In addition to sensing viral RNAs, RLRs are important regulators of a growing list of non-infectious immunopathologies that may result from an inappropriate host response to self RNA. RLR-mediated detection of viral RNA results in the mitochondrial antiviral signaling protein (MAVS)-dependent activation of antiviral signaling pathways that result in the expression of cytokines, interferons (IFNs) and interferon stimulated genes (ISGs). While these responses are critical for clearing viral infections, they are also deleterious in the context of autoimmunity. The reason for this is that many of the factors induced by RLRs are responsible for activating autoreactive T-cells. Thus, depending on the clinical symptoms, some patients may benefit from inhibition of the RLR/MAVS signaling pathways (e.g. T1D patients) whereas others may benefit from activating these pathways (HCV patients).
Technology Overview
Boston Children’s Hospital researchers have developed a novel peptide-based inhibitor of RLR-mediated signal transduction that could serve as a good molecular candidate for therapeutic modulation of the immune response.
Building off established knowledge of the various antiviral pathways that function in mammals, these researchers have created a peptide inhibitor of RLR-mediated signal transduction. This inhibitor provides the first molecular tool available to disrupt the functions of this family in human cells and may also be applicable for manipulating RLR pathways in mouse models of infection/autoimmunity. Moreover, the strategy used to design these RLR inhibitors may be adapted to generate peptides that activate the RLR pathways. Peptide activators of RLR signaling may prove particularly useful in treating chronic viral infections such as Hepatitis C Virus (HCV) as these viruses function to block antiviral signaling pathways.
Further Details:
Benefits
- Only existing treatment for inflammatory autoimmune diseases that are caused by inappropriate activation of antiviral responses.
- May improve disease outcomes while reducing the general and long-term side effects of TNF-a antagonists.
- This inhibitor provides the first molecular tool available to disrupt the functions of this family in human cells, and may also be applicable for manipulating RLR pathways in mouse models of infection/autoimmunity.
Applications
Peptide therapeutic to treat:
- Rheumatoid arthritis
- Inflammatory bowel disease
- Crohn’s disease
- Ulcerative colitis
