NITROXIDES FOR USE IN TREATING OR PREVENTING AMYLOID-RELATED DISEASES
Phamaceutical compositions are provided that are useful in treating amyloid protein-related diseases such as Alzheimer's disease. The compositions comprise a pharmaceutically acceptable carrier, and an effective therapeutic or prophylactic amount of a nitroxide antioxidant that downregulates one or more genes related to the amyloid-related disease. Methods are also provided for the use of the pharmaceutical compositions in the treatment or prevention of amyloid protein-related diseases. In a preferred embodiment, the nitroxide antioxidant is Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl), and the amyloid protein-related disease is Alzheimer's disease. In a preferred embodiment, the downregulated genes are genes related to inflammation or oxidative stress.
1 . A method for reducing serum levels of one or more amyloid proteins, comprising:
identifying an individual in need of reducing serum amyloid protein levels; and
administering to that individual an effective amount of a nitroxide antioxidant.
2 . The method of claim 1 , wherein the nitroxide antioxidant is 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl.
3 . The method of claim 1 , wherein the amyloid proteins are selected from a group consisting of serum amyloid P component precursor and serum amyloid A-1 protein precursor.
4 . The method of claim 1 , wherein the effective amount of a nitroxide antioxidant is within a range of 0.01-300 mg/kg.
5 . The method of claim 1 , wherein the effective amount of a nitroxide antioxidant is within a range of 0.1-250 mg/kg.
6 . The method of claim 1 , wherein the effective amount of a nitroxide antioxidant is within a range of 1-200 mg/kg.
7 . The method of claim 1 , wherein the effective amount of a nitroxide antioxidant is within a range of 2-150 mg/kg.
8 . The method of claim 1 , wherein the effective amount of a nitroxide antioxidant is within a range of 5-125 mg/kg.
9 . The method of claim 1 , wherein the effective amount of a nitroxide antioxidant is within a range of 7-100 mg/kg.
10 . The method of claim 1 , wherein the effective amount of a nitroxide antioxidant is within a range of 10-75 mg/kg.
11 . The method of claim 1 , wherein the effective amount of a nitroxide antioxidant is within a range of 15-30 mg/kg.
12 . A method for inhibiting the progression of disease associated with an amyloid protein, comprising:
identifying an individual affected by or at risk for amyloid protein-associated disease; and
administering to that individual an amount of a nitroxide antioxidant effective to alter expression of a gene associated with the amyloid protein-related disease.
13 . The method of claim 12 , wherein the amyloid protein-associated disease is Alzheimer's disease.
14 . The method of claim 12 , wherein the amyloid protein-associated disease is selected from the group consisting of rheumatoid arthritis, familial Mediterranean fever, Parkinson's disease, end-stage renal disease, juvenile chronic arthritis, psioratic arthropathy, ankylosing spondylitis, Behcet's syndrome, reactive arthritis, and Crohn's disease.
15 . The method of claim 12 , wherein the nitroxide antioxidant is 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl.
16 . The method of claim 12 , wherein the expression level of the gene is reduced.
17 . The method of claim 16 , wherein the gene is selected from a group consisting of genes encoding serum amyloid P-component precursor, serum amyloid A-1 protein precursor, JAI-1, cathepsin B, eukaryotic translation initiation factor 4E member 2, cyclooxygenase-1, and caspase 3.
18 . The method of claim 12 , wherein the expression level of the gene is increased.
19 . The method of claim 18 , wherein the gene is eukaryotic translation initiation factor 4E binding protein.
20 . The method of claim 12 , wherein the effective amount of a nitroxide antioxidant is within a range of 0.01-300 mg/kg.
21 . The method of claim 12 , wherein the effective amount of a nitroxide antioxidant is within a range of 0.1-250 mg/kg.
22 . The method of claim 12 , wherein the effective amount of a nitroxide antioxidant is within a range of 1-200 mg/kg.
23 . The method of claim 12 , wherein the effective amount of a nitroxide antioxidant is within a range of 2-150 mg/kg.
24 . The method of claim 12 , wherein the effective amount of a nitroxide antioxidant is within a range of 5-125 mg/kg.
25 . The method of claim 12 , wherein the effective amount of a nitroxide antioxidant is within a range of 7-100 mg/kg.
26 . The method of claim 12 , wherein the effective amount of a nitroxide antioxidant is within a range of 10-75 mg/kg.
27 . The method of claim 12 , wherein the effective amount of a nitroxide antioxidant is within a range of 15-30 mg/kg.
28 . A method for treating Alzheimer's disease, comprising:
administering to an Alzheimer's patient an amount of a nitroxide antioxidant effective to inhibit Alzheimer's plaque formation.
29 . The method of claim 28 , wherein the nitroxide antioxidant is administered in an amount effective to reduce serum levels of at least one protein related to plaque formation.
30 . The method of claim 29 , wherein the protein related to plaque formation is selected from a group consisting of serum amyloid P-component precursor, serum amyloid A-1 protein precursor, JAK-1, cathepsin B, eukaryotic translation initiation factor 4E member 2, cyclooxygenase-1, and caspase 3.
31 . The method of claim 28 , wherein the nitroxide antioxidant is administered in an amount effective to increase serum levels of at least one protein related to plaque formation.
32 . The method of claim 31 , wherein the protein related to plaque formation is eukaryotic translation initiation factor 4E binding protein.
33 . The method of claim 28 , wherein the effective amount of a nitroxide antioxidant is within a range of 0.01-300 mg/kg.
34 . The method of claim 28 , wherein the effective amount of a nitroxide antioxidant is within a range of 0.1-250 mg/kg.
35 . The method of claim 28 , wherein the effective amount of a nitroxide antioxidant is within a range of 1-200 mg/kg.
36 . The method of claim 28 , wherein the effective amount of a nitroxide antioxidant is within a range of 2-150 mg/kg.
37 . The method of claim 28 , wherein the effective amount of a nitroxide antioxidant is within a range of 5-125 mg/kg.
38 . The method of claim 28 , wherein the effective amount of a nitroxide antioxidant is within a range of 7-100 mg/kg.
39 . The method of claim 28 , wherein the effective amount of a nitroxide antioxidant is within a range of 10-75 mg/kg.
40 . The method of claim 28 , wherein the effective amount of a nitroxide antioxidant is within a range of 15-30 mg/kg.
41 . Use of a nitroxide antioxidant in the preparation of a medicament for reducing serum amyloid protein levels.
42 . Use of a nitroxide antioxidant in the preparation of a medicament for altering intracellular levels of one or more proteins associated with an amyloid protein-associated disease.
43 . Use of a nitroxide antioxidant in the preparation of a medicament for treating Alzheimer's disease.
44 . Use of a nitroxide antioxidant in the preparation of a medicament for inhibiting Alzheimer's plaque formation.