Endothelin-1–Induced Endoplasmic Reticulum Stress in Disease : Arjun Jain

Journal of Pharmacology and Experimental Therapeutics, 2013

Although the use of ET receptor antagonists has been useful in ameliorating disease pathology, there are certain draw- backs to consider. The use of ET antagonists has previously been associated with side effects, such as an increase in heart rate, facial flush, and/or facial edema (Fleisch et al., 2000). In addition, certain ET antagonists may interfere with anticoagulants, such as warfarin, and therefore pose a risk of thrombosis (Weber et al., 1999). These studies indicate the importance of only regulated antagonism of the ET receptor system as a therapeutic tool. 

An alternative strategy for prevention of ET-1–induced pathology would be to target the actual elevated levels of ET-1 in pathologic conditions.

At ET-traps Limited, we have developed an Fc-based fusion protein that has a very high binding affinity; in the pico molar range, which is higher than  ERAs that are already in clinical use.

Creating a Soluble Binder to Endothelin-1 Based on the Natural Ligand Binding Domains of the Endothelin-1 (G-Protein-Coupled) Receptor: Arjun Jain et al., International Journal of Peptide Research and Therapeutics, 2017

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Our PoC work (both in vitro and in vivo) has shown that the ET-traps are non- toxic or cytotoxic at the working concentration, which gives an efficacious effect.

In vitro

Endothelin-1 traps potently reduce pathologic markers back to basal levels in an in vitro model of diabetes; Arjun Jain et al.,  Journal of Diabetes & Metabolic Disorders, 2018

• ET- traps have efficacious effect on markers of pathology after both high endothelin-1 and high glucose treatment,
• High glucose induced expression of the markers of pathology tested is dependent on endothelin-1 

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In vivo 

 In vivo studies demonstrate that endothelin-1 traps are a potential therapy for type I diabetes; Arjun Jain et al.,  Journal of Diabetes & Metabolic Disorders, 2019  [Accepted, under Publication]

• Although ET-traps do not affect glucose levels, ET-traps have an efficacious, therapeutic effect on different factors of diabetic pathology, including diabetic cardiomyopathy, CKD, and other markers in the heart and kidney
   
• All markers of pathology return to basal, non-diabetic levels after treatment with ET-traps 

                                                                  AFFORDABLE, SIMPLE AND SAFE

• NON- TOXIC
• SIGNIFICANTLY DECREASE ELEVATED LEVELS OF ET-1 TO THE NORMAL PHYSIOLOGICAL LEVEL.
• HIGH BINDING AFFINITY
• IT IS A Fc-FUSION PROTEIN (FFP) AND SO HAS A LONGER SERUM HALF LIFE. 
• NON-IMMUNOGENIC : The FFPs can be modulated more easily so that the therapy does not elicit any negative immune reaction.
• COST EFFECTIVE
• ABLE TO HELP WITH BROAD RANGE OF DISEASES (elevated endothelin-1 levels)