Novel Pomegranate Oil Nano-Emulsions for the Prevention and Treatment of Neurodegenerative Diseases: The Case of Genetic CJD (P5.236)

OBJECTIVE: To develop safe long term preventive agents for neurodegenerative conditions. BACKGROUND: Neurodegenerative diseases are associated with progressive irreversible brain damage. Therefore, prevention of disease onset and advance by safe compounds that can be administered to subjects at risk or when first symptoms are noticable should be the main target of disease modifying research. Such at risk individuals are carriers of pathogenic mutations in key disease proteins, as is the case for mutant forms of the PrP protein, causing genetic Creutzfeldt-Jacob disease (gCJD).(gCJD). DESIGN/METHODS: To this effect and since sensitivity to oxidative stress plays a major role in neurodegenerative diseases, we treated our TgMHu2ME199K mice, which model for E200K PrP related gCJD, with Pomegranate seed oil (PSO) in its natural form or in a novel emulsified formulation (Nano-PSO). PSO comprises large concentrations of a unique conjugated polyunsaturated fatty acid, Punicic acid, considered as one of the strongest natural antioxidants. Young and asymptomatic mice, as well as older and already sick TgMHu2ME199K mice, were treated for several months either with PSO or with Nano-PSO. RESULTS: We show here that administration of large concentrations of PSO may delay disease presentation in young Tgs, and that lower doses of Nano-PSO significantly delayed disease onset in asymptomatic TgMHu2ME199K mice and postponed disease aggravation in already sick mice. Biochemical and pathological analysis revealed that while Nano-PSO treatment did not interfere with PrP accumulation, it reduced lipid oxidation and neuronal loss and restored neurogenesis, indicating a strong neuroprotective effect. CONCLUSIONS: Nano-PSO formulations may be beneficial to subjects suffering from diverse neurodegenerative conditions, including prion diseases. Most important, they are safe enough to be administrated for long periods of time to asymptomatic at risk individuals. Study Supported by: ISF and the Agnes Ginges for human Neurogenetics Disclosure: Dr. Gabizon has nothing to disclose. Dr. Mizrahi has nothing to disclose. Dr. Friedman-Levy has nothing to disclose. Dr. Larush has nothing to disclose. Dr. Frid has nothing to disclose. Dr. Binyamin has nothing to disclose. Dr. Feinstein has nothing to disclose. Dr. Dori has nothing to disclose. Dr. Ovadia has nothing to disclose. Dr. Ben-Hur has received personal compensation for activities with BrainWatch, Regenera Pharma. Dr. Magdassi has nothing to disclose.