Cyclodextrins as Emerging Therapies for Kidney Diseases: Focus on FSGS

Focal segmental glomerulosclerosis (FSGS) is a rare but severe kidney disease that scars the glomeruli, leading to proteinuria and progressive kidney damage. Although the underlying mechanisms of FSGS are complex, emerging evidence links the disease to disrupted cholesterol metabolism within kidney cells. This dysregulation can cause lipid accumulation in podocytes (the cells responsible for filtering blood), ultimately impairing kidney function. As a result, lipid modulation has become a target for new FSGS therapies.

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Cyclodextrins, a family of cyclic oligosaccharides, have gained attention for their ability to bind and modulate cholesterol in cell membranes. By extracting cholesterol from lipid-laden cells, cyclodextrins can potentially alleviate cellular stress and reduce inflammation—both critical factors in FSGS progression. Their ability to remove or redistribute cholesterol makes cyclodextrins particularly appealing for lipid-driven kidney diseases, as they offer a novel approach to reduce podocyte dysfunction and slow kidney damage.

Papers published

First papers in the field were published in 2018, the same year when FDA Approved Development of VAR 200 (HPBCD) for Treatment of FSGS.

Studies suggest that cholesterol accumulation contributes to kidney disease progression, including diabetic kidney disease, FSGS, and Alport Syndrome. In Alport mice, kidney cholesterol increased eight-fold, leading to inflammation and fibrosis, but treatment with hydroxypropyl-β-cyclodextrin (HPβCD) reduced these symptoms. HPβCD also improved proteinuria and kidney structure in other models, highlighting its therapeutic potential in lipid-driven kidney diseases.

Companies in the field

Several cyclodextrin-based therapies are under development, with notable applications in targeting cholesterol accumulation in kidney, liver, and cardiovascular diseases. ZyVersa Therapeutics Inc. is leading the charge in kidney disease research with its asset VAR-200, a proprietary hydroxypropyl-beta-cyclodextrin specifically designed to treat FSGS by removing excess cholesterol from kidney cells. Recently, ZyVersa announced progress in clinical trials , providing new hope for patients with FSGS. The promising results so far underscore VAR-200’s potential to become a first-in-class therapy for reducing kidney damage in patients with this challenging disease. Phase 2a clinical trial for Cholesterol Efflux Mediator??VAR 200 in patients with diabetic kidney disease is planned to begin H2-2024.

Oraxion Therapeutics , a company developing cyclodextrin polymer -based active ingredients also has an earlier stage program on FSGS using their asset.