Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital, 91120 Jerusalem, Israel; Medical School, The Hebrew University, Jerusalem, Israel.
Casali Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Neurobiol Dis. 2017 Dec;108:140-147. doi: 10.1016/j.nbd.2017.08.012. Epub 2017 Aug 25.
We have shown previously that Nano-PSO, a nanodroplet formulation of pomegranate seed oil, delayed progression of neurodegeneration signs when administered for a designated period of time to TgMHu2ME199K mice, modeling for genetic prion disease. In the present work, we treated these mice with a self-emulsion formulation of Nano-PSO or a parallel Soybean oil formulation from their day of birth until a terminal disease stage. We found that long term Nano-PSO administration resulted in increased survival of TgMHu2ME199K lines by several months. Interestingly, initiation of treatment at day 1 had no clinical advantage over initiation at day 70, however cessation of treatment at 9months of age resulted in the rapid loss of the beneficial clinical effect. Pathological studies revealed that treatment with Nano-PSO resulted in the reduction of GAG accumulation and lipid oxidation, indicating a strong neuroprotective effect. Contrarily, the clinical effect of Nano-PSO did not correlate with reduction in the levels of disease related PrP, the main prion marker. We conclude that long term administration of Nano-PSO is safe and may be effective in the prevention/delay of onset of neurodegenerative conditions such as genetic CJD.
我们之前已经证明，Nano-PSO（一种石榴籽油的纳米液滴制剂）在针对遗传朊病毒病模型的 TgMHu2ME199K 小鼠中进行了指定时间段的治疗后，可延缓神经退行性病变迹象的进展。在本研究中，我们从出生之日起至疾病终末期，用 Nano-PSO 自乳化制剂或平行的大豆油制剂对这些小鼠进行了治疗。我们发现，长期 Nano-PSO 给药可使 TgMHu2ME199K 品系的存活率提高数月。有趣的是，与第 70 天开始治疗相比，第 1 天开始治疗并没有临床优势，但是在 9 个月大时停止治疗会导致有益的临床效果迅速丧失。病理学研究表明，Nano-PSO 治疗可减少 GAG 积累和脂质氧化，表明其具有很强的神经保护作用。相反，Nano-PSO 的临床效果与疾病相关 PrP（主要朊病毒标志物）水平的降低无关。我们得出结论，长期给予 Nano-PSO 是安全的，并且可能有效预防/延缓神经退行性疾病（如遗传 CJD）的发生。
