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Biochem Biophys Res Commun. 2003 Oct 17;310(2):627-33.

EGCG corrects aberrant splicing of IKAP mRNA in cells from patients with familial dysautonomia.

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  • 1Laboratory for Familial Dysautonomia Research, Department of Biological Sciences, Fordham University, Bronx, NY, USA.


Familial dysautonomia (FD) is an autosomal recessive neurodegenerative disorder. The most prevalent causative mutation is a T-->C transition in a donor splice site of the IKBKAP transcript, resulting in aberrant splicing and a truncated protein. The mutation's position and leaky nature suggested that its impact might be moderated by altering the level of splice-regulating proteins. The reported ability of (-)-epigallocatechin gallate (EGCG), a polyphenol, to down-regulate the expression of hnRNP A2/B1, a trans-activating factor that encourages the use of intron-distal 5(') splice sites, prompted an evaluation of its effect on the IKBKAP transcript in FD-derived cells. EGCG reduces the level of hnRNP A2/B1 and increases the amounts of the wild-type IKBKAP-encoded transcript and functional protein. Combined treatment of cells with EGCG and tocotrienol, which upregulates IKBKAP transcription, results in a synergistic production of the functional gene product. These findings suggest the possible use of EGCG as a therapeutic modality for individuals with FD.

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