Drug repurposing for lupus nephritis therapy

Lupus nephritis management consists of an initial (induction) phase and a maintenance (extended) phase in which steroids are used in combination with another immunosuppressive medication. Current treatments are incompletely effective and associated with substantial toxicity.

Our compound X is a pharmacological agent already approved for human use in other medical indications. When orally administered, compound X can be repurposed to prevent or attenuate the development of lupus nephritis and, eventually, other SLE manifestations, without the toxicity and side effects associated with the continued use of corticosteroids and immunosuppressant drugs.

Oral bioavailability: > 90%; biological half-life: up to 48 h; excretion: feces and urine.

In vitro assays, compound X has been shown to reduce the expression of co-stimulation and maturation markers from inflammatory monocytederived dendritic cells.

Moreover, in the LN murine model (LZB/LZW F1 mice), oral administration of compound X after the beginning of disease (week 30 of age) was able to significantly delay the onset and to reduce the level of proteinuria (to improve renal function) compared to non-treated LZB/LZW F1 mice. This translated to: 1) preservation of weight with age; and 2) 100% survival compared to non-treated LZB/LZW F1 mice (8% survival) at the end of the study (330 days). All these results show that the technology is ready for clinical trials.

IP status: Patent application ongoing.