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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Article info
Publication history
Published online: June 27, 2021
Accepted:
June 18,
2021
Received in revised form:
June 11,
2021
Received:
March 10,
2021
Footnotes
Funding: The study was supported by the Prusiner-Abramsky research grant and by the Principal Investigator's personal grants.
Identification
Copyright
© 2021 Elsevier B.V. All rights reserved.
