Cholesterol chelator, HPβCD for renal diseases

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There is increasing evidence that accumulation of intracellular lipids in the kidney contributes to the pathogenesis and progression of kidney disease. Lipid accumulation is observed in both genetic and non-genetic origins of kidney disease. Data from animal models of three distinct kidney diseases demonstrate that 2-hydroxypropyl-βcyclodextrin decreases intracellular renal lipids, prevents structural damage to the kidney, and restores function.

Zyversa licensed worldwide rights to 2-HPβCD for the treatment of kidney disease based on these results. The research was led by Dr. Alessia Fornoni, Professor of Medicine and Chief, Katz Family Division of Nephrology and Hypertension, University of Miami Miller School of Medicine. A phase 2a study in patients with FSGS was scheduled to begin in 2020.

Lipid abnormalities are common in patients with chronic kidney disease, including high levels of cholesterol in the blood (hypercholesterolemia) and cholesterol accumulation within the kidney. Recent research suggests that it is the elevated cholesterol within the kidney, rather than that in the blood that contributes to the pathogenesis and progression of kidney diseases.

2-HPβCD significantly reduced total cholesterol in the kidney cortex compared with untreated diabetic mice. This was associated with a significant reduction in renal damage. Reducing intracellular renal lipids with 2-HPβCD, prevents glomerular damage and kidney dysfunction, suggesting that 2-HPβCD has potential to become a disease-modifying treatment option. Results have been consistent across in vitro and in vivo studies in animal models representing three different types of kidney disease (diabetic nephropathy, FSGS, and Alport Syndrome).

Abourt Zyversa:

ZyVersa is a clinical stage specialty biopharmaceutical company leveraging advanced proprietary technologies to develop first-in-class drugs. The clinical pipeline includes phase 2a-VAR 200, a cholesterol efflux mediator for treatment of an orphan renal disease, focal segmental glomerulosclerosis (FSGS), and a novel inflammasome inhibitor with potential for multiple inflammatory diseases.

The product pipeline is targeted to the $60+ billion anti-inflammatory market and the $13+ billion renal drug market. The lead renal drug candidate is 2-hydroxypropyl-beta-cyclodextrin (2HPβCD), a cholesterol efflux mediator demonstrated in preclinical studies to promote cholesterol removal from podocytes, a component of the kidney’s filtering system, slowing progression of podocyte injury and renal disease.

Read more:

Renal Lipids in the Pathogenesis of Kidney Disease, and the Role of 2-Hydroxypropyl-β-Cyclodextrin as
a Potential Treatment Option. https://www.zyversa.com/renal-lipids/white-paper-renal-lipids-in-the-pathogenesis-of-kidney-disease

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