Development of A Novel Multi-functional Compound for the Treatment of Autoimmune Disorders

Summary

• Approximately 23.5 million people suffer from an autoimmune disorders
• Autoimmune diseases are a family of more than 80 chronic, often debilitating and, in some cases, life-threatening illnesses
• Current treatments are severely lacking
• Biogenic molecules are an effective alternative to steroids and broad immunosuppressive drugs
• 3-HKA, a biogenic compound derived from tryptophan, was identified by Dr. Santambrogio and colleagues as a novel viable candidate for treating multiple autoimmune disorders
• Dr. Santambrogio and colleagues have designed and developed over 30 3-HKA analogs and are actively screening for novel analogs that mimic the anti-inflammatory activity of 3-HKA

Technical Overview

• Tryptophan, an amino acid commonly found in food, is used by dendritic cells (DCs) to produce kynurenines, which have immune-suppressing activities
• Using both in vitro and in vivo models, the researchers observed that treating cells with IFN-ɣ led to high levels of proinflammatory cytokines such as tumor necrosis factor (TNF) and IL-6
• 3-HKA was shown to inhibit major inflammatory pathways including STAT1/NF-κB and activated PKA-mediated immunosuppression
• 3-HKA significantly reduced the amount of inflammation, and infiltration of immune cells, in mouse models of psoriasis, nephrotoxic nephritis, and Crohn's disease
• Preliminary results indicate that 3-HKA was particularly abundant in breast and lung cancer cells, which suggests that cancer cells may produce this molecule to evade antitumor immune responses

Market Opportunity

• Roughly 8% of the American population is afflicted by an autoimmune disorder
• Current treatments for autoimmune disorders are lacking and often treat symptoms of disease rather than the root cause
• 3-HKA is a multi-functional compound that shows promising efficacy for treating autoimmune disorders
• Blocking 3-HKA also shows promising efficacy against cancer
• Dr. Santambrogio’s work paves the way for the development of novel molecules that mimic 3-HKA

Partnering Opportunity

Weill Cornell Medicine is seeking an industrial partner with deep domain expertise and a presence in the autoimmunity space to further develop novel compounds that mimic 3-HKA

Figure 1: Immunofluorescence of a lymph node shows lymphatic endothelial cells contain the enzyme (labeled in green) that generates 3-HKA.