A New Prednisone for Lupus Nephritis

Prednisone is often viewed as a necessary evil in the rheumatic diseases we treat. The appealing aspect of this drug is that it works quickly and effectively. It does, however, have many side effects. But there are certain situations, such as inflammatory myopathy, severe rheumatoid arthritis, and lupus nephritis, among others, that necessitate its use.

Researchers at the University of Nebraska have recognized this challenge, and in an attempt to address it, have developed a novel pro-drug of dexamethasone that passively targets the kidney, to be used in the treatment of lupus nephritis (Abstract #2789). They named their pro-drug ZSJ-0228, and tested it in an animal lupus nephritis model involving the use of female mice, whereby polyethylene glycol was conjugated to dexamethasone via hydrazone.

When compared to dose-equivalent daily dexamethasone treatment, use of this novel pro-drug improved mice survival and was also associated with significant normalization of albuminuria. Moreover, side effects typical of prednisone were not significantly observed (i.e. reduction in white blood cells, adrenal gland atrophy and osteopenia). It seems like the pro-drug primarily distributes in the kidneys, and is mainly sequestered by the intraglomerular mesangial cells and proximal tubule epithelial cells.

These animal studies certainly are exciting, and point to the possibility of development of a similar pro-drug to be used in humans. In the future, it may be interesting to see different forms of steroid being altered and modified to target specific sites of inflammation in the body such as the joints, muscle, and skin. Longer-term studies in humans would be helpful in identifying any possible steroid side effects over time, or in association with cumulative dosing.

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