Synergistic delay of gCJD aggravation by NPCs transplantation and Nano-PSO administration to sick TgMHu2ME199K mice

We have shown previously that both transplantation of neural precursor cells (NPCs), as well as administration of Nano-PSO into newborn and still asymptomatic TgMHu2ME199K mice, modeling for genetic CJD, significantly delayed presentation and advance of this fatal disease. In the present study, we tested the individual and combined effects of both treatments in mice already presenting initial signs of disease. We show that brain transplantation of NPCs at both initial (140 days) or advance state (230 days) arrested disease progression for 40 to 50 days, but subsequently disease scores rapidly climbed to those of untreated TgMHu2ME199K mice. Contrarily, administration of Nano-PSO from 140 days onward resulted in a steady but slower advance rate for the duration of treatment, resulting in longer survival of the mice. Combination of both treatments resulted in arrest of disease advance for a significantly higher period of time as compared to NPC transplantation alone, followed by a slower progression thereafter. Pathological examination of brains from the diverse groups indicate that while NPCs transplantation reduced the levels of disease related PrP accumulation, Nano-PSO administration extended survival of the transplanted NPCs, in addition to its general neuroprotective and antioxidant effect.