A University of Pittsburgh scientist has generated a potent hepatocyte growth factor (HGF) receptor (MET) agonist. Named META4, this agonist has been humanized and can be used to restore HGF-MET activity, reversing HGF dysfunction linked to several diseases. HGF can induce tissue growth and regeneration in a variety of tissues and organs including skin, liver, lung, and stem cells and any therapeutic that can restore HGF functionality has the potential to revolutionize treatment in a host of medical conditions.
Description
HGF is functional far beyond the liver; it can inhibit cell death, tissue necrosis and degradation, and is essential for glucose and fat metabolism and homeostasis. Nonalcoholic fatty liver disease can lead to hepatic dysfunction with a multitude of health complications including cardiovascular and kidney issues. A key part of hepatic dysfunction is the impairment of HGF interaction with the surface tyrosine kinase receptor, MET. Development of an agonist, META4, has led to restoration of HGF-MET activity and subsequent downstream effects. This agonist has the potential to restore HGF-MET activity and may provide a novel therapeutic approach in various forms of organ failure, hepatitis, and even other degenerative conditions like macular degeneration.
Applications
- Degenerative conditions
- Liver disease
- Age related macular degeneration (AMD)
Advantages
Currently there exists no effective therapy for a multitude of degenerative conditions including forms of hepatitis and AMD. Many of these diseases are increasing in prevalence and are considerable global health burdens. Previous strategies have included delivery of HGF to restore hepatic function, but this approach has failed due to poor pharmacokinetics and rapid clearance from the body. As such, there is a need to better understand the underlying biochemistry of hepatic dysfunction and develop strategies for reversal.
This novel agonist, META4, is stable and bioavailable, overcoming the issues of direct use of HGF. Additionally, it has been found to be a potent growth and survival factor in epithelia cells including hepatocytes and retinal pigmented epithelial cells. META4 can be converted to an antagonist to MET and potentially used in cancer therapy.
Invention Readiness
A potent MET agonist has been developed by immunizing mice with the extracellular portion of human MET and generated hybridomas that produce the monoclonal IgG1, META4. This has been humanized and found to be as active as the mouse version and is specific for humans and monkeys. In a humanized NASH model, META4 treatment was found to restore HGF-MET function and reinstate normal liver function due to HGF-MET signalling pathway being a key regulator of hepatic homeostasis.
IP Status
Patent Pending
