Methods and compositions for determining lipid peroxidation levels in oxidant stress syndromes and diseases
OwnerGarret A. Fitzgerald, Joshua Rokach +2inventors
InventorsGarret A. Fitzgerald, Joshua Rokach, Domenico Pratico, John O. Trojanowski
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Abstract
The invention includes methods useful for the diagnosis of Alzheimer's disease and the evaluation of enhanced levels of lipid peroxidation in a mammal. The methods utilize isoprostanes as sensitive and stable molecular markers for lipid peroxidation in a mammal. Methods of identifying compounds useful for the treatment of Alzheimer's disease or for reducing levels of lipid peroxidation in a mammal are also included. The invention also includes kits useful for the diagnosis of Alzheimer's disease and for the evaluation of levels of lipid peroxidation in a mammal.
Claims17
1-34. (Canceled)
A method of measuring the level of lipid peroxidation in a mammal suspected of having an oxidant stress syndrome or disease, wherein said oxidant stress syndrome or disease is selected from the group consisting of Alzheimer's disease, Amyotropic Lateral Sclerosis, Down's syndrome, and Parkinson's disease, said method comprising
- a) obtaining a first sample of a tissue or body fluid from said mammal;
- b) assessing the level of an isoprostane molecular marker for lipid peroxidation present in said first sample, wherein said isoprostane molecular marker is selected from the group consisting of iPF2α-III, iPF2α-VI, and 8,12-iso-iPF2α-VI;
- and
- c) comparing the level of said isoprostane molecular marker present in said first sample with the level of said isoprostane molecular marker present in a second sample of a tissue or body fluid obtained from an otherwise identical mammal which is not afflicted with an oxidant stress syndrome or disease, wherein an elevated level of said isoprostane molecular marker in said first sample relative to the level of said isoprostane molecular marker in said second sample, is indicative of an elevated level of lipid peroxidation in said mammal, thereby indicating the presence of an oxidant stress syndrome or disease in said mammal.
A method of diagnosing an oxidant stress syndrome or disease in a mammal, wherein said oxidant stress syndrome or disease is selected from the group consisting of Alzheimer's disease, Amyotropic Lateral Sclerosis, Down's syndrome, and Parkinson's disease, said method comprising
- a) obtaining a first sample of a tissue or body fluid from said mammal;
- b) assessing the level of said isoprostane molecular marker present in said first sample, wherein said isoprostane molecular marker is selected from the group consisting of iPF2α-III, iPF2α-VI, and 8,12-iso-iPF2-VI;
- and
- c) comparing the level of said isoprostane molecular marker present in said first sample with the level of said isoprostane molecular marker present in a second sample of a tissue or body fluid obtained from an otherwise identical mammal which is not afflicted with an oxidant stress syndrome or disease, wherein an elevated level of said isoprostane molecular marker in said first sample relative to the level of said isoprostane molecular marker in said second sample, is indicative of an elevated level of lipid peroxidation in said mammal, thereby indicating the presence of an oxidant stress syndrome or disease in said mammal.
A method of identifying a compound useful for reducing the level of an isoprostane molecular marker for lipid peroxidation said method comprising
- a) measuring the level of an isoprostane molecular marker for lipid peroxidation in either a sample of a tissue or body fluid obtained from a first mammal prior to administering said compound, or, in a sample of a tissue or body fluid obtained from an otherwise identical second mammal which is not to be administered said compound;
- b) administering said compound to said first mammal;
- c) thereafter measuring the level of said isoprostane molecular marker in a tissue or body fluid obtained from said first mammal;
- and
- d) comparing the level of said isoprostane molecular marker in c) with the level of said isoprostane molecular marker measured in a), wherein when the level of said isoprostane molecular marker measured in c) is reduced relative to the level of said isoprostane molecular marker in a), a compound useful reducing the level of an isoprostane molecular marker for lipid peroxidation in a mammal is identified.
A kit for diagnosing an oxidant stress syndrome or disease, wherein said oxidant stress syndrome or disease is selected from the group consisting of Alzheimer's disease, Amyotropic Lateral Sclerosis, Down's syndrome, and Parkinson's disease, said kit comprising
- a) a sample container for carrying a tissue or body fluid sample from said mammal;
- b) a solution for use in extraction of an isoprostane molecular marker for lipid peroxidation from said tissue or body fluid sample obtained from said mammal;
- c) a negative control solution of said isoprostane molecular marker of lipid peroxidation present at a concentration of about the concentration of said isoprostane molecular marker present in a tissue or body fluid sample of a mammal which is not afflicted with an oxidant stress syndrome or disease, wherein said oxidant stress syndrome or disease is selected from the group consisting of Alzheimer's disease, Amyotropic Lateral Sclerosis, Down's syndrome, and Parkinson's disease;
- d) a positive control solution of said isoprostane molecular marker of lipid peroxidation present at a concentration of about the concentration of said isoprostane molecular marker in a tissue or body fluid sample of a mammal which is afflicted with an oxidant stress syndrome or disease, wherein said oxidant stress syndrome or disease is selected from the group consisting of Alzheimer's disease, Amyotropic Lateral Sclerosis, Down's syndrome, and Parkinson's disease;
- e) an antibody directed against an isoprostane molecular marker for lipid peroxidation;
- and
- f) an instructional material.
A kit for measuring the level of an isoprostane molecular marker for lipid peroxidation in a tissue or body fluid sample obtained from a mammal, said kit comprising
- a) a sample container for carrying a tissue or body fluid sample from said mammal;
- b) a solution for use in extraction of an isoprostane molecular marker of lipid peroxidation from said tissue or body fluid sample obtained from said mammal;
- c) a negative control solution of said isoprostane molecular marker of lipid peroxidation present at a concentration of about the concentration of said isoprostane molecular marker present in a tissue or body fluid sample of a mammal which is not afflicted with an oxidant stress syndrome or disease, wherein said oxidant stress syndrome or disease is selected from the group consisting of Alzheimer's disease, Amyotropic Lateral Sclerosis, Down's syndrome, and Parkinson's disease;
- d) a positive control solution of said isoprostane molecular marker of lipid peroxidation present at a concentration of about the concentration of said isoprostane molecular marker in a tissue or body fluid sample of a mammal which is afflicted with an oxidant stress syndrome or disease, wherein said oxidant stress syndrome or disease is selected from the group consisting of Alzheimer's disease, Amyotropic Lateral Sclerosis, Down's syndrome, and Parkinson's disease;
- e) an antibody directed against an isoprostane molecular marker for lipid peroxidation;
- and
- f) an instructional material.
Dependencies are inferred from the claim text.