Problem

The liver sinusoidal clearance system (LSCS) is responsible for eliminating the majority of circulating macromolecular waste, inflammatory mediators, toxins, and therapeutic agents. Excessive hepatic clearance limits the efficacy of therapies, including chemotherapies and vaccines. In contrast, insufficient clearance of metabolic toxins contributes to chronic inflammation, fibrosis, metabolic dysfunction, and aging‑related disease. Existing therapies primarily target downstream disease manifestations, such as hyperglycemia or inflammation, rather than the upstream failure of systemic detoxification and waste handling. There is a critical need for therapies that can selectively and reversibly modulate hepatic clearance capacity

Solution

Researchers at The Ohio State University have developed a first‑in‑class, modular platform that enables precise and reversible control of the liver sinusoidal clearance system by using a synthetic amino acid nanofiber, Amino Acid Compound 2 (AAC2), and its protein complexes, most notably AAC2–IGFBP4 (insulin‑like growth factor binding protein 4). AAC2 can function as an inhibitor of hepatic clearance by selectively suppressing scavenger/clearance receptors activities in endothelial cells of LSCS, thereby reducing premature uptake and elimination of circulating macromolecules. However, when AAC2 is in complex with IGFBP4, it activates the clearance system and upregulates scavenger and immune‑complex clearance receptors. In genetically obese mice, treatment with AAC2–IGFBP4 increased the expression of endothelial markers of LSCS including clearance receptors, leading to a remarkable reduction in HbA1c levels and hyperinsulinemia, while improving insulin sensitivity and glucose tolerance, and reducing hyperphagia and body weight

Applications

• Treatment of degenerative diseases, including aging, metabolic disease (Type 2 diabetes, insulin resistance, obesity), inflammatory and autoimmune conditions, fibrosis, neuroinflammation (caused by dementia, Parkinson, drug addiction type 3 diabetes), and complication of infectious diseases
• Use as adjuvant therapy to improve the efficacy and reduce the toxicity of cancer treatments and other therapeutic biologicals, pharmacological agents, gene therapies, and vaccines
• Detoxification strategies following sepsis, infection, pollutant, or toxin exposure

Advantages

• First-in-class approach targeting the liver sinusoidal clearance system
• Bidirectional control: same platform enables both inhibition and activation
• Modular nanofiber platform adaptable to multiple proteins
• Broad disease relevance across multiple indications

Seeking opportunities for out-licensing and collaboration