ET-traps is a novel therapeutic that targets pathologically elevated endothelin-1 levels in the body, bringing endothelin-1 and various markers of heart and kidney function back to non-disease levels without side effects.
We have discovered a potent therapy for chronic kidney disease, cardiovascular disease, and other diseases associated with pathologically elevated ET-1 levels such as diabetes and neurological disorders, with a low cost, low dosage drug with no side effects.
~10% of the world population suffers from chronic kidney disease, majority in developing world unable to afford treatment - Every year there are ~1 million deaths from untreated kidney disease
There are limited treatment options. Studies have shown significant benefit of targeting the endothelin system even when added to maximum tolerated dose of RAS blockers (current standard of care). However, ERAs can't be used as they have side effects like fluid retention. Thus, ET-traps can address this large unmet need.
ET-traps would help further slow down disease progression, reduce proteinuria, inflammation, fibrosis, cardiovascular risk (by improving lipid profile and blood pressure). It would improve GFR, reduce glomerulosclerosis and tubulointerstitial fibrosis by preventing ER stress.
Endothelins contribute to neurophysiology and cerebrovascular regulation. ET-1, ET-3, ETA receptors and ETB receptors are expressed by vascular, neuronal and glial cells . ET-1 is also abundant in macrophages, leukocytes and fibroblasts causing inflammation in many of the neurological diseases.
Cardiovascular diseases are the number one cause of death globally and one of the costliest diseases for health care systems. ET-1 is the most potent vasoconstrictor with long lasting action and is the most abundant isoform in the human cardiovascular system. It causes sustained vasoconstriction, inflammation, fibrosis, hypertrophy and proliferation.
Diabetes can cause many complications. Acute complications can include diabetic ketoacidosis, hyperosmolar hyperglycemic state, or death. Serious long-term complications include cardiovascular disease, stroke, chronic kidney disease, foot ulcers, and damage to the eyes.
Currently available therapies are mainly limited to insulin and glucose control medications. However most of the fatalities and the healthcare costs related to diabetes are from complications like heart and kidney disease. ET-traps helps bring heart and kidney function to non disease levels as shown in our PoC work.
The ET-traps approach to diabetes provides therapeutic synergy for (i) bringing back the pathologically elevated levels of endothelin-1 and (ii) repair of damage caused to the vital organs (long-term complications).
Pre-eclampsia is a pregnancy-induced hypertensive disorder characterized by proteinuria and widespread maternal endothelial dysfunction. It remains one of the most common disorders in pregnancy and one of the leading causes of maternal and fetal morbidity. The hypertension in the disease pathology is induced through the production of excess endothelin-1 and the only cure currently is the delivery of the baby.