Methods and compositions for altering cell function
The present invention relates to compositions and methods for altering cell function. In particular, the present invention provides compositions comprising selenium (e.g., SEL-PLEX) and methods of using the same (e.g., as a therapeutic and/or prophylactic treatment). Additionally, the present invention demonstrates that specific forms of selenium (e.g., SEL-PLEX), when administered to a subject, possess the ability to alter (e.g., reduce) gene expression in various tissues (e.g., compared to expression in subjects not administered selenium).
1 . A method of treating a subject comprising:
a) providing:
i) a subject; and
ii) a composition comprising selenium; and
b) administering said composition to said subject under conditions such that the expression of Gadd45b is reduced in said subject compared to expression of Gadd45b in a subject not administered said composition comprising selenium.
2 . The method of claim 1 , wherein said expression of Gadd45b is reduced in two or more tissues of said subject.
3 . The method of claim 2 , wherein said two or more tissues are selected from the group consisting of cerebral cortex tissue, liver tissue, intestinal tissue and skeletal muscle tissue.
4 . The method of claim 3 , wherein said subject displays a greater than two-fold reduction in liver tissue-specific and skeletal muscle tissue-specific Gadd45b gene expression.
5 . The method of claim 1 , wherein said expression of Gadd45b is reduced in cerebral cortex tissue and one or more non-cerebral cortex tissues of said subject.
6 . The method of claim 5 , wherein said one or more non-cerebral cortex tissues are selected from the group consisting of liver tissue, intestinal tissue and skeletal muscle tissue.
7 . The method of claim 1 , wherein said composition comprising selenium comprises SEL-PLEX.
8 . The method of claim 7 , wherein said expression of Gadd45b is reduced in cerebral cortex tissue, liver tissue, intestinal tissue and skeletal muscle tissue.
9 . The method of claim 8 , wherein said expression is reduced one fold or greater in said tissues.
10 . The method of claim 7 , wherein said composition comprising SEL-PLEX comprises one or more other forms of selenium.
11 . The method of claim 10 , wherein said one or more forms of selenium comprises sodium-selenite.
12 . The method of claim 1 , wherein said composition comprising selenium is co-administered with an antioxidant.
13 . The method of claim 12 , wherein said antioxidant is selected from the group consisting of alkylated diphenylamines, N-alkylated phenylenediamines, phenyl-α-naphthylamine, alkylated phenyl-α-naphthylamine, dimethyl quinolines, trimethyldihydroquinolines, hindered phenolics, alkylated hydroquinones, hydroxylated thiodiphenyl ethers, alkylidenebisphenols, thiopropionates, metallic dithiocarbamates, 1,3,4-dimercaptothiadiazole, an oil soluble copper compound, NAUGALUBE 438, NAUGALUBE 438L, NAUGALUBE 640, NAUGALUBE 635, NAUGALUBE 680, NAUGALUBE AMS, NAUGALUBE APAN, Naugard PANA, NAUGALUBE TMQ, NAUGALUBE 531, NAUGALUBE 431, NAUGALUBE BHT, NAUGALUBE 403, NAUGALUBE 420, ascorbic acid, tocopherols, alpha-tocopherol, a sulfhydryl compound, sodium metabisulfite, N-acetyl-cysteine, lipoic acid, dihydrolipoic acid, resveratrol, lactoferrin, ascorbic acid, ascorbyl palmitate, ascorbyl polypeptide, butylated hydroxytoluene, retinoids, retinol, retinyl palmitate, tocotrienols, ubiquinone, a flavonoid, an isoflavonoid, genistein, diadzein, resveratrol, grape seed, green tea, pine bark, propolis, IRGANOX, Antigene P, SUMILIZER GA-80, beta-carotene, lycopene, vitamin C, vitamin E, and vitamin A.
14 . The method of claim 1 , wherein said composition comprising selenium is administered in such a way so as to provide between 25 and 400 μg of selenium to said subject each day.
15 . The method of claim 1 , wherein said composition comprising selenium is administered in such a way so as to provide 200 μg of selenium to said subject each day.
16 . A method of treating a subject comprising:
a) providing:
i) a subject; and
ii) a composition comprising selenium; and
b) administering said composition to said subject under conditions such that the expression of a tau kinase is reduced in the brain of said subject compared to expression of said tau kinase in a subject not administered said composition comprising selenium.
17 . The method of claim 16 , wherein said tau kinase is selected from the group consisting of glycogen synthase kinase-3-beta (GSK-3β) and cyclin dependent kinase 5 (Cdk-5).
18 . The method of claim 16 , wherein said subject is selected from the group consisting of a subject having a tauopathy, a subject displaying signs or symptoms or pathology indicative of a tauopathy, a subject suspected of displaying signs or symptoms or pathology indicative of a tauopathy, a subject at risk of displaying signs or symptoms or pathology indicative of a tauopathy, and a subject at risk of a tauopathy.
19 . The method of claim 16 , wherein said tauopathy is selected from the group consisting of Alzheimer's disease (AD), Pick's disease (PiD), progressive supranuclear palsy, corticobasal degeneration, argyrophilic grain disease, and familial frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17-tau).
20 . The method of claim 16 , wherein reducing said tau kinase gene expression reduces phosphorylation of tau in said subject.
21 . The method of claim 16 , wherein reducing the expression of said tau kinase in the brain of said subject reduces the presence of neurofibrillary tangles in said subject.
22 . The method of claim 16 , wherein said composition comprising selenium comprises SEL-PLEX.
23 . The method of claim 22 , wherein said composition comprising SEL-PLEX comprises one or more other forms of selenium.
24 . The method of claim 23 , wherein said one or more forms of selenium comprises sodium-selenite.
25 . The method of claim 16 , wherein said composition comprising selenium is co-administered with an antioxidant.
26 . The method of claim 25 , wherein said antioxidant is selected from the group consisting of alkylated diphenylamines, N-alkylated phenylenediamines, phenyl-α-naphthylamine, alkylated phenyl-α-naphthylamine, dimethyl quinolines, trimethyldihydroquinolines, hindered phenolics, alkylated hydroquinones, hydroxylated thiodiphenyl ethers, alkylidenebisphenols, thiopropionates, metallic dithiocarbamates, 1,3,4-dimercaptothiadiazole, an oil soluble copper compound, NAUGALUBE 438, NAUGALUBE 438L, NAUGALUBE 640, NAUGALUBE 635, NAUGALUBE 680, NAUGALUBE AMS, NAUGALUBE APAN, Naugard PANA, NAUGALUBE TMQ, NAUGALUBE 531, NAUGALUBE 431, NAUGALUBE BHT, NAUGALUBE 403, NAUGALUBE 420, ascorbic acid, tocopherols, alpha-tocopherol, a sulfhydryl compound, sodium metabisulfite, N-acetyl-cysteine, lipoic acid, dihydrolipoic acid, resveratrol, lactoferrin, ascorbic acid, ascorbyl palmitate, ascorbyl polypeptide, butylated hydroxytoluene, retinoids, retinol, retinyl palmitate, tocotrienols, ubiquinone, a flavonoid, an isoflavonoid, genistein, diadzein, resveratrol, grape seed, green tea, pine bark, propolis, IRGANOX, Antigene P, SUMILIZER GA-80, beta-carotene, lycopene, vitamin C, vitamin E, and vitamin A.
27 . The method of claim 16 , wherein said composition comprising selenium is co-administered with an Alzheimer's therapeutic.
28 . The method of claim 27 , wherein said Alzheimer's therapeutic is selected from the group consisting of a NMDA antagonist, an ACHE inhibitor, and a metal chelator.
29 . The method of claim 28 , wherein said NMDA antagonist is memantine.
30 . The method of claim 28 , wherein said ACHE inhibitor is tacrine, donepezil, rivastigmine, or galantamine.
31 . The method of claim 28 , wherein said metal chelator is clioquinol.
32 . The method of claim 31 , wherein said clioquinol chelates zinc and copper.
33 . The method of claim 16 , wherein said composition comprising selenium is administered in such a way so as to provide between 25 and 400 μg of selenium to said subject each day.
34 . The method of claim 16 , wherein said composition comprising selenium is administered in such a way so as to provide 200 μg of selenium to said subject each day.