Department of Neurology
Hadassah University Hospital
Summary:
We have shown recently that administration of Nano-PSO (GranaGard), a nanodroplet formulation of pomegrante seed oil, to TgMHu2ME199K , a Tg mice line modeling for genetic prion disease from 3 to 10 months of age delayed disease advance significantly. In the present study, we aimed to determine the effects of life span administration of GranaGard to such transgenic mice, and concomitantly search for the mechanism of action of this compound vis a vis neurodegeneration markers. To this effect, we administrated GranaGard or a parallel Soya oil formulation to TgMHu2ME199K mice from their day of birth to their ethically approved terminal stage. Mice was followed periodically for their clinical status and sacrificed either at designated points and subsequently brains were processed for pathological, biochemical and molecular analysis. We found that continuous administration of GranaGard resulted in increased survival of TgMHu2ME199K mice by several months, as compared to untreated or Nano-Soya treated Tg mice, without any adverse effects. In addition, while Nano-PSO administration had no effect on the rate or levels of disease related PrP accumulation, it induced a significant reduction in alcian blue/pas staining for sugar amyloids, which is a common feature in all neurodegenerative conditions. Most interestingly, Nano-PSO treated brains presented reduced levels of caspase immunostaining and increased levels of Nestin expressing endogenous stem cells, indicating a massive neuroprotective effect. Biochemical analysis of brain samples of mice treated with GranaGard but not with PSO of Nano-Soya present measurable levels of CLA, a natural Punicic acid metabolite shown to have neuroprotective and anti- amyloid properties.
Conclusions:
We conclude that long term administration of Nano-PSO is both safe and effective for the prevention/delay of progression of genetic CJD in mice. Its mechanism of action, neuroprotective and independent for PrP accumulation suggests this may be the case also in other neurodegenerative conditions.