Cytoprotection/Inflammation
FibroGen is developing a series of HIF-PHI designed to stabilize HIF and elicit a rapid, multi-factorial, cytoprotective response for treating a variety of conditions resulting from ischemic injury and associated inflammation. Experimental research has shown that treatment with HIF-PHI can reduce tissue damage and preserve organ function resulting from an initial ischemic event (e.g., heart attack, acute kidney injury, stroke) or from subsequent reperfusion injury. FibroGen is also evaluating HIF-PHI for chronic cytoprotection, especially for the treatment of neurodegenerative diseases.
Acute Cytoprotection
Protecting healthy tissue immediately following an initial ischemic event, preservation of organ function, and prevention of organ failure are the therapeutic goals of using cytoprotective HIF-PHI in acute clinical settings. FibroGen is targeting the following therapeutic areas:
- Myocardial infarction: Preclinical research has shown that a single dose of HIF-PHI administered after an experimentally induced heart attack reduces damage to heart muscle. FibroGen is also exploring the potential for HIF-PHI therapy administered on a chronic basis to promote remodeling of heart tissue and prevent subsequent heart failure. Potential HIF-mediated cardioprotective mechanisms include adenosine receptor signaling, iNOS upregulation, and ATP preservation. Read more
- Acute Kidney Injury: Preclinical studies conducted by FibroGen and academic collaborators have demonstrated that HIF-PHI mitigate ischemia reperfusion injury and subsequent acute kidney injury, leading to preservation of kidney function. Potential HIF-mediated renoprotective factors include EPO, HO-1, and VEGF. Read more
- Stroke: Neuroprotective effects of EPO are well documented. FibroGen has reported neuroprotective effects of HIF-PHI in transient and permanent models of ischemic stroke including reduction in infarct size and preservation of motor function. The data suggest that the protective benefits of HIF-PHI involve important HIF-mediated responses beyond EPO. Read more
Chronic Cytoprotection
FibroGen is exploring the ability of HIF-PHI to protect tissues in chronic inflammatory and degenerative conditions of the heart, kidney and central nervous system. Beneficial effects of chronic therapy with recombinant human EPO have been reported in diseases such as multiple sclerosis, schizophrenia, and chronic kidney disease. Other HIF-mediated mechanisms in addition to EPO, such as suppression of inflammatory mediators (e.g., IL-6, MCP-1, and COX2), are expected to provide a more comprehensive cytoprotective treatment approach. Read more
