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IN VITRO STUDY TO ASSESS THE POTENTIAL OF SHORT CHAIN FATTY ACIDS (SCFA) AS THERAPEUTIC AGENTS FOR ALZHEIMER'S DISEASE
Author(s) -
Ann Dipika Binosha Fernando Warnakulasuriya Mary,
RaineySmith Stephanie Ruth,
Martins Ian J.,
Martins Ralph N.
Publication year - 2014
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2014.05.1083
Subject(s) - butyrate , propionate , chemistry , in vitro , cell , cell culture , toxicity , biochemistry , biology , genetics , organic chemistry , fermentation
Background: Alzheimer’s disease (AD) is a neurodegenerative disorder pathologically characterized by extracellular senile plaques, primarily composed of polymerized amyloid-beta (Abeta) peptides. There is currently no cure for this devastating disease that represents one of today’s major healthcare challenges due to its severe socio-economic burden. The huge potential offered by human adult stem cells for the treatment of various neurodegenerative disorders is supported by a number of ongoing clinical trials, however the impact of these cells on Abeta amyloid pathology has not been yet investigated in a pre-clinical study. Methods: We evaluated the impact of a repeated intravenous delivery of clinical grade human ischemic tolerant adult mesenchymal stem cells (itMSC) on Abeta amyloid pathology in a mouse model of AD.Results: Ten weeks of itMSC treatment safely reduced cerebral Abeta plaques in aged amyloid-depositing Alzheimeric mice (w 30 %, p< 0.0001). Plaque-associated microglia significantly increased in density, suggesting that these cells contributed to plaque removal following itMSC treatment. The impact of itMSC delivery on recovering brain dysfunction in Alzheimeric mice is currently being investigated using in vivo functional neuroimaging. Conclusions: Our pre-clinical results indicate that adult itMSC can decrease Abeta amyloid pathology in a mouse model of AD. As revealed in the current pre-clinical study, the combination of safety and efficacy to remove amyloid plaques offered by itMSC, together with successfully completed safety phase I clinical trials, may put itMSC as a perspective candidate for treating Abeta amyloid pathology in AD.