12-Lipoxygenase and 12-HETE
12-lipoxygenase (12-LOX) is an enzyme in the arachidonic acid (AA) pathway that oxidizes AA resulting in the production of 12-HETE. High 12-LOX activity and 12-HETE production have been linked to numerous syndromes and diseases, with elevated levels of serum 12-HETE having potential implications as a predictive biomarker for T1D. Following discovery of selective 12-LOX inhibitors, Veralox is taking a novel approach to treat these diseases with initial focus on heparin-induced thrombocytopenia (HIT), HIT with thrombosis (HITT) and type 1 diabetes (T1D). Both of these diseases have inadequate treatments and Veralox aims to improve outcomes for these patients in need.
Heparin-Induced Thrombocytopenia (HIT) and HIT with Thrombosis (HITT)
HIT and HITT are life-threatening diseases that occur in up to 3% percent of patients receiving heparin. HIT/HITT arises from an aberrant immune response to heparin. This response leads to the activation of platelets, which triggers blood clots, potentially resulting in deadly heart attacks, stroke or loss of limbs. Currently, the only FDA-approved drug on the market to treat HIT/HITT does not address the underlying cause of the disease and carries a significant risk of severe bleeding. Veralox’s first-in-class therapeutic, VLX-1005, addresses the underlying cause of this immune-driven blood clotting. Targeting platelet 12-LOX inhibits the production of 12-HETE, a proinflammatory metabolite shown to play an important role in platelet activation. By addressing the underlying pathology of HIT/HITT, VLX-1005 addresses a serious unmet clinical need and should greatly improve clinical outcomes.
Type 1 Diabetes (T1D)
Veralox is developing a disease-modifying therapy for Type 1 diabetes, another immune-driven pathology. In Type 1 diabetes patients, an abnormal immune response results in damage and destruction to insulin-producing pancreatic β-cells. Inflammatory signals increase the expression of 12-LOX, leading to an overabundance of 12-HETE. 12-HETE stresses β-cells leading to a reduction in insulin production.
By inhibiting 12-LOX in the pancreas and shutting down production of 12-HETE, insulin β-cells are preserved and able to function properly. With a significant number of T1D patients, particularly new-onset T1D patients having functional β-cells, Veralox’s approach holds promise to sustain insulin production in these patients.