Methods for Treating, Ameliorating, and Preventing Nephropathy/Nephritis

Method for protecting against nephropathy/nephritis through topical administration of a vitamin D3 analog, producing systemic therapeutic effects potentially beneficial in protein-losing nephropathy, lupus nephritis, diabetic nephropathy, focal segmental glomerulosclerosis (FSGS), and genetic nephropathies.
Problem:
Protein-losing nephropathy, lupus nephritis (a manifestation of Systemic lupus erythematosus), diabetic nephropathy, FSGS, and genetic nephropathies are disorders that damage the glomerular filtration barrier, resulting in proteinuria and progressive renal scarring. Despite differing etiologies, these disorders converge on a common pathway of chronic glomerular injury that progresses to chronic kidney disease and, ultimately, renal failure. More targeted, disease-modifying therapies that avoid broad systemic immunosuppression remain a significant unmet medical need.
Solution:
This technology leverages topical delivery of the vitamin D₃ analog MC903 which has an established safety profile in humans to modulate kidney inflammation through a skin-kidney axis. Applied to the skin, MC903 activates the vitamin D receptor promoting skin-derived bile acid synthesis that signals through Farnesoid X Receptor, a mechanism distinct from broad systemic immunosupresion.

In murine models of lupus nephritis, topical MC903 significantly reduced proteinuria and tubular damage, improved urine protein score even after disease onset. The protection occurred without altering anti-dsDNA antibody levels, suggesting a mechanism distinct from broad systemic immunosuppression. The approach offers a non-invasive, skin-targeted strategy with systemic benefit, positioning MC903 as a potential therapeutic platform for lupus nephritis and other proteinuric kidney diseases.
Advantages:

• Kidney-protective efficacy
• Effectiveness after disease onset
• Novel mechanism of action
• Non-invasive
• MC903’s extensive human safety data

Stage of Development:

• Preclinical Discovery

Topical MC903 protects against proteinuria in Spontaneous Lupus Model NZB x NZW F1. Mice were treated with topical application of MC903 starting at Week 24 (3 times/week; every other week).
Intellectual Property:

• Provisional Filed

Desired Partnerships:

• License
• Co-development

Docket #25-10866