TREATMENT OF MULTIPLE SCLEROSIS BY INHIBITION OF ALLOGRAFT INFLAMMATORY FACTOR-1
Methods are disclosed for treating multiple sclerosis comprising administering an agent that reduces expression and/or activity of Allograft inflammatory factor-1 (Aif-1) in a subject and for screening for such agents.
1 . A method of treating multiple sclerosis in a subject comprising administering to the subject an agent in an amount effective to reduce expression and/or activity of Allograft inflammatory factor-1 (Aif-1) in a subject.
2 . The method of claim 1 , wherein Aif-1 expression and/or activity is reduced in lymphocytes.
3 . The method of claim 1 , wherein Aif-1 expression and/or activity is reduced in macrophages and/or microglia.
4 . The method of claim 1 , wherein the agent is an antisense molecule, a ribozyme, or an RNA interference (RNAi) molecule, and the agent reduces expression of Aif-1.
5 . The method of claim 1 , wherein the agent is a small molecule, an antibody, an antibody fragment, or an aptamer, and the agent reduces the activity of Aif-1.
6 . The method of claim 1 , wherein the agent does one or more of reduce infiltration in the central nervous system by leukocytes and/or CD4 + T cells and/or microglia; reduce CD4 + T cell activation; reduce pro-inflammatory cytokine expression, and reduce demyelination.
7 . The method of claim 1 , wherein the agent reduces expression of Aif-1.
8 . The method of claim 1 , wherein the agent reduces the activity of Aif-1.
9 . A method for screening for an agent that treats multiple sclerosis in a subject, the method comprising determining whether or not the agent reduces expression and/or activity of Allograft inflammatory factor-1 (Aif-1), wherein an agent that reduces expression and/or activity of Aif-1 is a candidate for treating multiple sclerosis.
10 . The method of claim 9 , wherein the agent reduces Aif-1 expression and/or activity in lymphocytes.
11 . The method of claim 9 , wherein the agent reduces Aif-1 expression and/or activity in macrophages and/or microglia.
12 . The method of claim 9 , wherein the method is carried out using a cell culture based assay that uses an enzyme-linked immunosorbent assay (ELISA) or Western blots to assess Aif-1 levels in cellular lysates or in the cell culture medium.
13 . The method of claim 9 , wherein Aif-1 activity is assessed using a Nuclear Factor kappa B (NFkB) reporter assay.
14 . The method of claim 9 , wherein AiF-1 levels are assessed in serum, plasma, tissue homogenates, cell culture supernatants or another biological fluid.
15 . The method of claim 9 , wherein the agent does one or more of reduce infiltration in the central nervous system by leukocytes and/or CD4 + T cells and/or microglia; reduce CD4 + T cell activation; reduce pro-inflammatory cytokine expression, and reduce demyelination.
16 . The method of claim 9 , wherein the agent reduces expression of Aif-1.
17 . The method of claim 9 , wherein the agent reduces the activity of Aif-1.