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Beneficial effects of a nano formulation of pomegranate seed oil, GranaGard, on the cognitive function of multiple sclerosis patients

  • Panayiota Petrou
    Affiliations
    Multiple sclerosis Center and cell therapies Unit, Unit and Laboratory of Neuroimmunology and The Agnes-Ginges Center for Neurogenetics, Hadassah University Hospital, Jerusalem
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  • Ariel Ginzberg
    Affiliations
    Multiple sclerosis Center and cell therapies Unit, Unit and Laboratory of Neuroimmunology and The Agnes-Ginges Center for Neurogenetics, Hadassah University Hospital, Jerusalem
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  • Orli Binyamin
    Affiliations
    Multiple sclerosis Center and cell therapies Unit, Unit and Laboratory of Neuroimmunology and The Agnes-Ginges Center for Neurogenetics, Hadassah University Hospital, Jerusalem
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  • Dimitrios Karussis
    Correspondence
    Corresponding author.
    Affiliations
    Multiple sclerosis Center and cell therapies Unit, Unit and Laboratory of Neuroimmunology and The Agnes-Ginges Center for Neurogenetics, Hadassah University Hospital, Jerusalem
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      Highlights

      • No adverse events were recorded during a 3-month treatment of patients with MS with GranaGard, a brain targeting nano-formulation of PSO.
      • GranaGard administration seems to induce short-term beneficial effects and to improve/stabilize cognitive disability in MS patients.
      • Putative mechanisms of action of GranaGard are mostly related to its strong anti-oxidative effects.

      Abstract

      Background

      Though often neglected, cognitive impairment is a common feature of multiple sclerosis in 43–70% of patients. None of the novel MS treatment seems to substantially affect or restore cognitive disability in MS. GranaGard (Granalix Bio Technologies LTD) is a food supplement shown to prevent neuronal death in several animal models of neurological diseases. Capsules of GranaGard comprise a self-emulsion nano formulation of pomegranate seed oil (PSO). This oil contains 80–90% of Punicic Acid (PA), one of the strongest natural antioxidants. In animal experiments, administration of GranaGard results in conjugation with linoleic acid (CLA), the main metabolite of PA, which is a well-known neuroprotective agent.

      Aims

      To investigate whether GranaGard administration has an effect on the cognitive state of MS patients.

      Methods

      This is a single center, randomized double blind clinical trial that started in May 2018. The study included 30 MS patients; half of them (Group-A) were given GranaGard for the first three months and then placebo pills containing soybean oil for additional three months. Patients in Group-B received placebo for the first three months, and GranaGard for the following three months. GranaGard was administrated in addition to their immunomodulatory MS-treatments. Subsequently, all patients received GranaGard for additional six months. Patients were required to visit the neurologist at baseline (inclusion, visit 1) and at 3 months after treatment-initiation at each cycle of the trial (visits 2 and 3). During the follow up visits, clinical and cognitive examinations were performed, including Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC: 25 ft walking test, 9 PEG hole test & PASAT). Cognitive tests included The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery: 1) Symbol Digit Modalities Test (SDMT); 2) California Verbal Learning Test – Second Edition (CVLT-II); 3) and Brief Visuospatial Memory Test – Revised (BVMT-R). Cognitive outcomes were normalized to the healthy population and expressed as z-scores, depended on age, gender and education. Short quality of life and fatigue questionnaires (SF-12, MFIS-5) were also provided by the participants.

      Results

      No serious adverse effects, related to the product, were observed during the study period. All patients receiving GranaGard reported a ‘’positive‘’ effect in their ADL while using the product. While there were no significant differences in the clinical parameters of disability (EDSS scores) between the treatment groups, there was a trend of beneficial effect of GranaGard, on the verbal testing during the first 3-month period of treatment. The z score for CVLT-II, significantly increased (from 0.891 to 1.415, p = 0.012, Wilcoxon rank test) at 3-months in the group of patients who were treated with GranaGard, as compared to baseline. A similar (but not statistically significant) trend was seen also in the BVMTr testing during the same 3 months-period, whereas there was no change in the SDMT. The overall average z-score of all three cognitive functions was significantly improved in the three months of Granagard treatment (-0.0077 at 3 months vs 0.462 at baseline, p = 0.034, Wilcoxon rank test). During the same 3-months period there were no significant changes in the placebo-treated group. For the patients receiving GranaGard in the initial 3 months, the value of z score of CVLT-II remained high (z = 1.415) also at the following three months (while they received placebo), suggesting a longer lasting effect for at least 3 months after discontinuation of the drug.

      Conclusion

      This is the first study in which GranaGard, a brain targeted nano-formulation of PSO, was tested in humans. Our results in this small pilot, controlled trial provide indications that GranaGard administration to MS patients might improve/stabilize cognitive disability. Larger studies with longer duration, are needed to confirm these initial observations.

      Keywords

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