Targeting EGFR and IL-6 for the treatment of liver fibrosis and insulin resistance

This technology identifies EGFR and IL-6 as therapeutic targets for the treatment of liver fibrosis and glucose intolerance.

Unmet Need: Targeting chronic inflammation in MASH progression

Current treatment strategies for metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis rely primarily on lifestyle modifications, often inadequate and ineffective for patients with advanced disease. There are currently no FDA-approved therapies for MASH. Existing therapeutic approaches primarily target metabolic dysfunctions, but the pathogenesis of the disease is multifactorial, with chronic inflammation also playing an important role. Regulatory T (Treg) cells help maintain tissue homeostasis by limiting inflammation and promoting repair, representing a potential therapeutic modality for halting or reversing disease progression.

The Technology: Crosstalk between Treg cells and hepatic fibroblasts as a therapeutic target

The technology identifies a functional relationship between regulatory T (Treg) cells and tissue injury in metabolic dysfunction-associated steatohepatitis (MASH). Treg cells drive hepatic glucose intolerance and liver fibrosis through the secretion of amphiregulin (Areg), an EGFR-ligand that activates hepatic fibroblasts and increases their production of interleukin-6 (IL-6), a pro-inflammatory cytokine. Inhibition of EGFR and IL-6 expression within hepatic stellate cells leverages this relationship to slow the progression of tissue injury and fibrosis. Therefore, the crosstalk between Treg cells and hepatic fibroblasts represents a therapeutic target for the treatment of chronic liver disease and glucose resistance.

This technology has been validated in vitro and in vivo.

Applications:

• Biomarker for metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis
• Treatment for liver fibrosis, glucose intolerance, and MASH
• Research tool for understanding the involvement of Treg cells in liver fibrosis

Advantages:

• Unexplored therapeutic target
• Addresses chronic inflammation
• Alleviates glucose intolerance
• Identifies amphiregulin and IL-6 as biomarkers for chronic lung disease

Lead Inventor:

Nicholas Arpaia, Ph.D.

Patent Information:

Patent Pending (WO/2024/158827)

Related Publications:

• Savage TM, Fortson KT, de los Santos-Alexis K, Oliveras-Alsina A, Rouanne M, Rae SS, Gamarra JR, Shayya H, Kornberg A, Cavero R, Li F, Han A, Haeusler RA, Adam J, Schwabe RF, Arpaia N. “Amphiregulin from regulatory T cells promotes liver fibrosis and insulin resistance in non-alcoholic steatohepatitis.” Immunity. 2024 Feb 13;57(2):303-318.e6.

Tech Ventures Reference:

• IR CU23130

• Licensing Contact: Cynthia Lang