Novel Treatment for Fibrosis

University of Pittsburgh, Tuskegee University and The University of North Carolina (UNC) researchers have developed a cocktail of chemokine peptides, a class of signaling molecules, to reduce fibrosis. This novel therapeutic approach regulates key biological pathways implicated in fibrosis. Unlike many existing treatments which address the symptoms of fibrosis, this treatment strategy targets the underlying causes of the disease. The resulting positive outcomes could include prevention of long-term health complications and a decrease in early mortality.

Description

Fibrosis, the result of excessive extracellular matrix (ECM) deposition, can impact any organ scarred from chronic disease or traumatic injury. Fibrosis can result in painful symptoms, organ failure and mortality. Fibrosing disease contributes to 45% of deaths in the United States. In the body, fibroblasts are the primary producers of ECM, with chemokines playing an influential role in fibroblast-ECM production. Key to this process is the role of transforming growth factor-beta (TGF-) in promoting fibroblast production. This novel treatment, containing either single chemokines or a cocktail of chemokines, can reduce TGF--stimulated fibroblast product and provide hope to many of the millions of people living with fibrosis.

Applications

- Organ fibrosis
- Myocardial infarction (MI)
- Systemic sclerosis

Advantages

The role of chemokines in angiogenesis is impacted by the presence (ELR+) or absence (ELR-) of an ELR motif containing Glu-Leu-Arg. ELR+ chemokines (including CXCL2, CXCL8, and CXCL12), are pro-angiogenic; while ELR- chemokines (including CXCL4, CXCL9, and CXCL11), are mostly angiostatic and may inhibit fibrosis, but can hinder wound healing. Using this novel strategy, the synergistic effects of custom chemokine peptide cocktails inhibit excess ECM production, preventing fibrosis.

Invention Readiness

In vitro studies were carried out using primary human dermal fibroblasts treated with TGF- as a model for fibrosis. They were treated with either single chemokines or cocktails of chemokines to observe impacts on biomarkers of fibrosis. Treatment with ELR- chemokines and chemokine cocktails significantly downregulated COL1A1 and TNC expression in TGF-β-activated, but not quiescent fibroblasts. Some ELR+ chemokines (like CXCL8) could also downregulate biomarkers of fibrosis, demonstrating the potential of chemokines either as single agents or in cocktails to inhibit fibrosis. Further work is now needed to optimize the exact cocktail of chemokines required to treat organ fibrosis. There is also potential to explore if benefits could be gained by tailoring the treatment to each patient, providing personalized therapy.

IP Status

https://patents.google.com/patent/US20190298802A1