IVIG MODULATION OF CHEMOKINES FOR TREATMENT OF MULTIPLE SCLEROSIS, ALZHEIMER'S DISEASE, AND PARKINSON'S DISEASE
The present invention provides methods for providing a prognosis of treatment of diseases associated with inflammatory disease of the brain, including MS, e.g., relapsing-remitting multiple sclerosis (RRMS), Alzheimer's disease, and Parkinson's disease using molecular markers that are shown to be overexpressed or underexpressed in patients treated with intravenous immunoglobulins (IVIG). Also provided are methods to identify compounds that are useful for the treatment or prevention of MS, e.g., relapsing-remitting multiple sclerosis (RRMS), Alzheimer's disease, and Parkinson's disease.
1 . A method of providing a prognosis of Parkinson's disease in a subject treated with intravenous immunoglobulin (IVIG), the method comprising the steps of:
(a) contacting a biological sample from the subject treated with IVIG with a reagent that specifically binds to at least one marker selected from the group consisting of the nucleic acid and corresponding protein sequences shown in Table 3a, Table 3b, and Table 4; and
(b) determining whether or not the marker is overexpressed or underexpressed in the sample; thereby providing a prognosis for Parkinson's disease in a subject treated with IVIG.
2 . The method of claim 1 , wherein the reagent is an antibody.
3 . The method of claim 2 , wherein the antibody is monoclonal.
4 . The method of claim 1 , wherein the reagent is a nucleic acid.
5 . The method of claim 1 , wherein the reagent is an RT PCR primer set.
6 . The method of claim 1 , wherein the sample is a blood sample.
7 . The method of claim 6 , wherein the blood sample comprises T cells.
8 . The method of claim 1 , wherein the sample is cerebrospinal fluid.
9 . The method of claim 1 , wherein said at least one marker is a chemokine.
10 . The method of claim 9 , wherein said chemokine is selected from the group consisting of CXCL3, CXCL5, CCL13, and XCL2.
11 . A method of identifying a compound that prevents or treats Parkinson's disease, the method comprising the steps of:
(a) contacting a compound with a sample comprising a cell that expresses a marker selected from the group consisting of the nucleic acid and corresponding protein sequences shown in Table 3a, Table 3b, Table 3c, Table 3d, and Table 4; and
(b) determining the functional effect of the compound on the marker, thereby identifying a compound that prevents or treats Parkinson's disease.
12 . The method of claim 11 , wherein the functional effect is an increase or decrease in expression of the marker.
13 . The method of claim 11 , wherein the functional effect is an increase or decrease in activity of the marker.
14 . The method of claim 11 , wherein the compound is a small molecule.
15 . The method of claim 11 , wherein the compound is a siRNA.
16 . The method of claim 11 , wherein the compound is a ribozyme.
17 . The method of claim 11 , wherein the compound is an antibody.
18 . A method of treating or preventing Parkinson's disease in a subject, the method comprising the step of administering to said subject an effective amount of an antibody which binds a chemokine selected from the group consisting of CXCL5, CXCL3, and CCL13, wherein said effective amount is sufficient to inactivate chemokine cell signaling, thereby treating or preventing Parkinson's disease.
19 . A method of treating or preventing Parkinson's disease in a subject, the method comprising the step of administering to said subject an effective amount of an antibody which binds a chemokine receptor selected from the group consisting of receptors for CXCL5, CXCL3, and CCL13, wherein said effective amount is sufficient to inactivate said chemokine receptor, thereby treating or preventing Parkinson's disease.
20 . A method of treating or preventing Parkinson's disease in a subject, the method comprising the step of administering to said subject an effective amount of an antibody which binds to a XCL2 chemokine receptor, wherein said effective amount is sufficient to activate said XCL2 chemokine receptor, thereby treating or preventing Parkinson's disease.