Efficacy and Safety Study of EGCG/Tocotrienol in 18 Patients With Splicing-mutation-mediated Cystic Fibrosis (CF)

* Working Hypothesis: EGCG and Tocotrienol can act as genetic modifiers and increase the level of correctly spliced CFTR transcripts. * Aims of the Study: To determine in patients with CF if oral administration of EGCG and Tocotrienol, both separate and in combination, modify CFTR splicing towards normal splicing as evaluated by improved Transepithelial Potential Difference (TEPD) assessment of chloride secretion. To assess the effect of EGCG and Tocotrienol, both separate and in combination, on (1) additional TEPD measures of ion channel activity, (2) levels of correctly spliced CFTR mRNA in nasal mucosa, (3) cytokine levels in sputum and (4) changes in pulmonary function over the course of the study. * Potential Implications to Medicine: Alternative splicing mechanisms are a common cause of genetic disease as \~15% of all known human mutations result in defective pre-mRNA splicing. Therapies based on augmenting the levels of full length or fully functioning proteins may have a substantial impact on the treatment of patients with genetic diseases. * Contribution of the expected outcome to society Today genetic diseases can be treated but not healed. This proposal may be a step in the direction of finding a cure for patients carrying splicing mutations.