Grape Derived Polyphenols

Researchers at the Mount Sinai School of Medicine in New York have investigated grape derived polyphenol extract (GDPE) as a potential treatment for Huntington's disease. They found promising results in a cell model, a drosophila model, and the R6/2 mice.

In previous studies, the authors investigated the bioavailability of GDPE and found that although it is metabolized in the gut, it does cross the blood brain barrier and can be detected in the brain.

The researchers have also studied GDPE as a potential Alzheimer's treatment and found that it interferes with aggregation of the protein associated with the disease. GDPE is also an antioxidant and metal chelator.

Using a PC-12 cell model with 103 CAG repeats, they found that protein aggregation and oxidative damage were both reduced. In a drosophila model, lifespan was significantly extended.

GPDE was administered to the R6/2 mice in a dosage of 100 mg/kg/day GSPE (equivalent to 500 mg per day in humans). Motor performance as measured by the rotarod was improved compared to untreated control mice. Lifespan was extended 8.3 percent.

Which mechanism or mechanisms - antioxidant effects, suppression of aggregation, metal chelation or something else - leads to the protective effects is not yet clear. There is no resveratrol in the grapes used to make the extract used in the study so that it is not a possibility. (Resveratrol is known to upregulate SIRT1 which is associated with lifespan extenstion.)

The authors recommend that GDPE be considered for clinical trials. "Our studies demonstrated strong evidence of preclinical efficacy of GSPE in HD treatment, and provide impetus for the application of GSPE for human clinical testing."

The study was funded by Polyphenols, Inc. who supplied the extract.

Marsha Miller, Ph.D.
Potential Application of Grape Derived Polyphenols in Huntington's Disease

Jun Wang, Cathie M. Pfleger, Lauren Friedman, Roselle Vittorino, Wei Zhao, Xianjuan Qian, Lindsay Conley, Lap Ho, Giulio M. Pasinetti

Huntington's disease (HD) is a progressive neurodegenerative disorder associated with selective neuronal cell death. Abnormal aggregation of huntingtin protein with polyQ expansion has been shown to be causally linked to HD. Grape seed polyphenolic extract (GSPE) is a natural compound that has previously been shown to interfere with aggregations of proteins involved in neurological disorders, such as amyloid beta peptides (Aβ) and Tau protein. In this study we found that GSPE treatment significantly inhibits polyQ aggregation in phaeochromocytoma (PC)-12 cell line containing an ecdysone-inducible protein comprising the first 17 amino acid of huntingtin plus 103 glutamines fused with enhanced GFP. In vivo feasibility studies using the Q93httexon1 drosophila model of HD, we extended our in vitro evidence and found that flies fed with GSPE had a significantly improved lifespan compared to the control flies. Using the R6/2 rodent model of HD, we found that oral administration of 100 mg/kg/day GSPE (equivalent to 500mg per day in human) significantly attenuated the motor skill decay as well as extended the lifespan in the R6/2 mice relative to vehicle-control mice. Collectively, our studies strongly suggest that GSPE might be able to modulate the onset and/or progression of HD.

Translational Neuroscience 2010 Jun 1;1(2):95-100