University of Pittsburgh, Tuskegee University and The University of North Carolina (UNC) researchers have developed a library of small peptides that can act as chemokine agonists or antagonists. These peptides could allow for selective regulation of a variety of chemokine signaling pathways involved in conditions including myocarditis and tissue fibrosis. These novel peptides could provide hope for many patients by tackling the underlying pathogenesis rather than only symptom management.
Description
Upregulation of the chemokine CXCL10, via CXCL10-CXCR3 signaling is beneficial as an angiostatic and anti-fibrotic chemokine in the wound healing period following myocardial infarction (MI) and can reverse fibrosis pathogenesis (when scar-like tissue replaces healthy tissue). CXCL10-CXCR3 signaling has been implicated as a contributing factor to myocarditis, and through in silico prediction-based functional peptide design a library of small peptides have been identified to either enhance or inhibit CXCL10-CXCR3 signaling. Targeting this signaling pathway could be a novel therapeutic approach to several medical conditions, including terminal idiopathic pulmonary fibrosis, for improved patient quality of life and outcomes.
Applications
1. Myocarditis 2. Organ Fibrosis 3. Myocardial Infarction (MI)
Advantages
Current treatments for organ fibrosis are limited, with transplantation often the only viable treatment to reverse fibrosis. Given the limited availability of transplantable organs, a therapy to reverse fibrosis is an unmet clinical need. Ischemic heart disease is the most common cause of death globally, and myocarditis, a clinical syndrome that can result in heart failure, affects millions. Research found CXCL10-CXCR3 signaling plays a vital role in the pathogenesis of these conditions. This novel approach uses small peptides which could be delivered via inhalation to directly impact on the CXCL10-CXCR3 signaling. Additionally, these peptide-based therapies are more likely to show higher potency and have fewer toxic effects.
Invention Readiness
In silico prediction-based peptides that mimic the CXCR3 ligand and initiate CXCL10-CXCR3 signaling, were identified. In vitro studies have demonstrated some of these peptides can act as agonists and others as antagonists to the CXCL10-CXCR3 signaling pathway. Preliminary data suggest this class of peptides will have increased efficacy at low doses, potentially translating to increased survival and tolerance, along with a lower cost of production.
IP Status
https://patents.google.com/patent/US20170000852A1; https://patents.google.com/patent/US20160022872A1; https://patents.google.com/patent/US9872889B2; https://patents.google.com/patent/US8734775B2
