Methods and compositions for treating metabolic disorders
First Claim
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1. A method of treating or preventing a disorder characterized by mitochondrial dysfunction in a subject, the method comprising administering to the subject a therapeutically effective amount of a cytoskeleton modulator.
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Abstract
The present invention provides methods of treating of disorders characterized by defective mitochondrial activity. In particular compounds of the present invention can be used in the treatment metabolic diseases and neurodegenerative diseases. The methods are also useful to increase oxidative phosphorylation or to decrease reactive oxygen species (ROS) production in a subject in need thereof.
38 Citations
52 Claims
- 1. A method of treating or preventing a disorder characterized by mitochondrial dysfunction in a subject, the method comprising administering to the subject a therapeutically effective amount of a cytoskeleton modulator.
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40. A method for identifying compounds that enhance mitochondrial function comprising (i) assaying for the effect of one or more compounds on (a) OXPHOS gene expression and (b) mitochondrial function;
- and (ii) correlating the effect with a compound'"'"'s enhancement of mitochondrial function, wherein an increase in OXPHOS gene expression and an increase in mitochondrial function is indicative of a compound that enhances mitochondrial function.
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41. A method for identifying compounds for treating a disorder characterized by mitochondrial dysfunction in a subject comprising (i) assaying for the effect of one or more compounds on (a) OXPHOS gene expression and (b) mitochondrial function;
- and (ii) correlating the effect with a compound'"'"'s ability to treat said disorder, wherein an increase in OXPHOS gene expression and an increase in mitochondrial function is indicative of a compound useful for treating said disorder.
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42. A method for determining compounds that are contraindicated in a subject, comprising (i) assaying for the effect of one or more compounds on (a) cellular dehydrogenase activity and (b) cell viability;
- and (ii) correlating the effect with contraindication of a compound, wherein a decrease in cellular dehydrogenase activity absent a decrease in cell viability indicates that the compound is contraindicated for said subjects.
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43. A method for determining two or more compounds that are contraindicated for joint administration to a subject comprising (i) assaying for the effect of two or more compounds on (a) cellular dehydrogenase activity and (b) cell viability;
- and (ii) correlating the effect with contraindication of joint administration, wherein two or more compounds that each decrease cellular dehydrogenase activity absent a decrease in cell viability indicates that the two or more compounds are contraindicated when jointly administered to a subject.
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44. A kit comprising a plurality of primer pairs wherein each primer pair comprises a first nucleic acid sequence and a second nucleic acid sequence which first nucleic acid sequence hybridizes under stringent conditions to a first strand of a target sequence, and which second nucleic acid sequence hybridizes under stringent conditions to a second strand of a target sequence, wherein the target sequence is selected from a group consisting of the following:
- (a) Mt-Atp6, (b) Mt-Atp8, (c) Mt-Co1, (d) Mt-Co2, (e) Mt-Co3, (f) Mt-Cytb, (g) Mt-Nd1, (h) Mt-Nd2, (i) Mt-Nd3, (j) Mt-Nd4, (k) Mt-Nd41, (l) Mt-Nd5, (m) Mt-Nd61, (n) Atp5a1, (o) Atp5c1, (p) Atp5o, (q) Cox5b, (r) Cox7a2, (s) Cyc1, (t) Hspc051, (u) Ndufa5, (v) Ndufb5, (w) Sdhd, (x) Uqcrb, and (y) Uqcrc1.
- View Dependent Claims (45, 46, 47)
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48. A method of detecting levels of at least 2 OXPHOS genes, comprising:
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(1) providing one or more target sequences selected from the following;
(a) Mt-Atp6, (b) Mt-Atp8, (c) Mt-Co1, (d) Mt-Co2, (e) Mt-Co3, (f) Mt-Cytb, (g) Mt-Nd1, (h) Mt-Nd2, (i) Mt-Nd3, (j) Mt-Nd4, (k) Mt-Nd41, (l) Mt-Nd5, (m) Mt-Nd61, (n) Atp5a1, (o) Atp5c1, (p) Atp5o, (q) Cox5b, (r) Cox7a2, (s) Cyc1, (t) Hspc051, (u) Ndufa5, (v) Ndufb5, (w) Sdhd, (x) Uqcrb, and (y) Uqcrc1,(2) providing the plurality of primers that hybridize under stringent conditions to a target sequence from step (1) (3) amplifying target sequences using primers, (4) amplifying the sequences of step (3) using 2 nucleic acid sequences that are complementary to at least 1 portion of the primers of step (2), wherein one nucleic acid sequence is linked to a binding moiety, and one nucleic acid sequence is phosphorylated, (5) identifying the amplification products of step (4) by hybridization to a nucleic acid sequence that is complementary to a portion of the amplification product, wherein nucleic acid sequence is covalently linked to a detectable moiety. - View Dependent Claims (49)
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- 51. The method of claim 51, wherein said detectable moiety is a microsphere.
Specification