Prurisol Summary

Prurisol is more effective than conventional therapies in human psoriatic tissue xenografts

» Prurisol (10 mg/kg PO twice/ day x 21 days)

» 84% reduction in lesion appearance

» 99% reduction in lesions based on histology

» 96% reduction in serum PRINS

» 87% reduction in serum IL-20

» No reoccurrence of lesions within 180 days

» Methotrexate (7.5 mg/kg IP once/ day x 5 days)

» 63% reduction in lesion appearance

» 76% reduction in lesions based on histology

» 48% reduction in serum PRINS

» 46% reduction in serum IL-20

» Lesions reoccurred in 61 days

Prurisol is a small molecule, acting on the principles of immune stimulation and PRINS reduction that has been found to be effective against psoriasis in animal models, both in induced psoriasis as well as a xenograft model with human psoriatic tissue.

Details

Prurisol was studied in mice that were irradiated with 350 Rads whole body to suppress graft rejection, and then engrafted with human psoriatic tissue by inserting human psoriatic tissue under the skin using a trocar. Groups of ten mice were treated with Prurisol orally for 21 days with either 10 mg/kg Prurisol once/ day or 10 mg/kg Prurisol twice/day, or with 7.5 mg/kg methotrexate IP once/day, or untreated mice as controls. The mice were followed for 180 days. Endpoints were skin appearance, based on a score of 0 for normal appearance to 10 for severe lesion, histological observations, also based on a score of 0 for normal appearance to 10 for severe lesion, PRINS RNA in psoriatic lesions, and blood IL-20 levels. For these parameters, Prurisol was compared to controls and methotrexate.

In a second experiment, groups of 10 immunocompetent CD-1 mice were treated with one or two doses of 10 mg/kg Prurisol daily or 3 mg/kg efalizumab SC once per week for 3 weeks. CD4+ and CD8+ lymphocyte counts were also measured by flow cytometry and compared to efalizumab. Prurisol significantly reduced all psoriatic endpoints measured relative to controls


In addition, psoriasis did not recur during the study period with the higher dose of Prurisol whereas with methotrexate, psoriasis recurred after an average of 61 days. Treatment with Prurisol caused less reduction in CD4+ lymphocyte counts than did efalizumab.  Weight loss in the treated animals was within acceptable limits.

Prurisol given at 10 mg/kg twice/day was shown to be more effective than methotrexate in reducing psoriatic skin lesions in a human xenograft model. In addition, Prurisol can be given orally and is well-tolerated.