Methods of treating or preventing neurological diseases

Abstract

The present disclosure provides a method for treating an inflammatory neurological disease comprising administering a population of cells enriched for STRO-1+ cells and/or progeny thereof and/or soluble factors derived therefrom.

1 . A method for treating or preventing an inflammatory neurological disease, the method comprising administering to the subject a population of cells enriched for STRO-1 +  cells and/or progeny thereof and/or soluble factors derived therefrom. 
     
     
         2 . The method of  claim 1 , wherein the inflammatory neurological disease is associated with or caused by a T cell response to an inflammatory stimulus. 
     
     
         3 . The method of  claim 1  or  2  comprising administering a population of cells enriched for STRO-1 bright  cells and/or progeny thereof and/or soluble factors derived therefrom. 
     
     
         4 . The method of any one of  claims 1  to  3 , wherein the inflammatory neurological disease is selected from the group consisting of multiple sclerosis, systemic lupus erythematosus, Guillain-Barre syndrome, Lambert-Eaton myasthenic syndrome, myasthenia gravis, transverse myelitis, leukodystrophy and progressive multifocal leukoencephalopathy. 
     
     
         5 . The method of any one of  claims 1  to  4 , wherein the disease is systemic lupus erythematosus. 
     
     
         6 . The method of any one of  claims 1  to  4 , wherein the disease is multiple sclerosis. 
     
     
         7 . The method of  claim 6 , wherein the disease is a chronic progressive form of multiple sclerosis or a relapsing-remitting form of multiple sclerosis. 
     
     
         8 . The method of any one of  claims 1  to  7 , wherein the population enriched for STRO-1 +  cells and/or progeny thereof and/or soluble factors derived therefrom are administered systemically. 
     
     
         9 . The method of any one of  claims 1  to  8 , wherein the disease is a relapsing-remitting disease and the population enriched for STRO-1 +  cells and/or progeny thereof and/or soluble factors derived therefrom are administered during disease relapse to prevent or delay relapse of the disease. 
     
     
         10 . The method of any one of  claims 1  to  9 , comprising administering an amount of the population enriched for STRO-1 +  cells and/or progeny thereof and/or soluble factors derived therefrom effective to increase the number of regulatory T (Treg) cells in the subject and/or at the site of pathogenesis of the disease. 
     
     
         11 . The method of any one of  claims 1  to  10 , comprising administering between 2×10 6  to 8×10 6  STRO-1 +  cells and/or progeny thereof per kg. 
     
     
         12 . The method of any one of  claims 1  to  11 , comprising administering between 3×10 6  to 6×10 6  STRO-1 +  cells and/or progeny thereof per kg. 
     
     
         13 . The method of any one of  claims 1  to  12  comprising administering a low dose of STRO-1 +  cells and/or progeny thereof. 
     
     
         14 . The method of  claim 13 , wherein the low dose of STRO-1 +  cells and/or progeny thereof comprises between 0.1×10 6  and 3×10 6  STRO-1 +  cells and/or progeny thereof per kg. 
     
     
         15 . The method of  claim 14 , wherein the low dose of STRO-1 +  cells and/or progeny thereof comprises about 3×10 6  STRO-1 +  cells and/or progeny thereof per kg. 
     
     
         16 . The method of any one of  claims 1  to  15 , wherein the population enriched for STRO-1 +  cells and/or progeny thereof and/or soluble factors derived therefrom are administered once weekly or less often. 
     
     
         17 . The method of any one of  claims 1  to  15 , wherein the population enriched for STRO-1 +  cells and/or progeny thereof and/or soluble factors derived therefrom are administered once every four weeks or less often. 
     
     
         18 . The method of any one of  claims 1  to  17 , wherein the population enriched for STRO-1 +  cells and/or progeny thereof are genetically-engineered to express a molecule to block stimulation of T cells and/or the soluble factors are from such genetically-modified cells. 
     
     
         19 . The method of any one of  claims 1  to  18 , wherein the population enriched for STRO-1 +  cells and/or progeny thereof and/or soluble factors therefrom are administered with a compound to block stimulation of T cells. 
     
     
         20 . The method of any one of  claims 1  to  19 , wherein the population enriched for STRO-1 +  cells and/or progeny cells are autogeneic or allogeneic and/or the soluble factors are derived from autogeneic or allogeneic cells. 
     
     
         21 . The method of any one of  claims 1  to  19 , wherein the population enriched for STRO-1 +  cells and/or progeny cells have been culture expanded prior to administration and/or prior to obtaining the soluble factors. 
     
     
         22 . A method for preventing an immune response in response to an antigen, the method comprising administering to the subject a population of cells enriched for STRO-1 +  cells and/or progeny thereof and/or soluble factors derived therefrom. 
     
     
         23 . The method of  claim 22 , wherein the immune response is a T cell-mediated immune response. 
     
     
         24 . The method of  claim 23 , wherein the T cell-mediated immune response comprises T cell proliferation. 
     
     
         25 . The method of any one of  claims 22  to  24 , wherein the T cell-mediated immune response is suppressed in response to a specific antigen and a T cell-mediated immune response in response to another antigen is not suppressed. 
     
     
         26 . The method of any one of  claims 22  to  25 , wherein the subject has previously raised an immune response to the antigen and the population, progeny and/or soluble factors suppress a further immune response to the antigen. 
     
     
         27 . The method of  claim 26 , comprising administering the population, progeny and/or soluble factors after the subject raises an immune response to the antigen to thereby prevent a further immune response to the antigen. 
     
     
         28 . The method of any one of  claims 22  to  27 , wherein the immune response is suppressed for at least about 24 days following administration of the population of cells enriched for STRO-1 +  cells and/or progeny thereof and/or soluble factors derived therefrom. 
     
     
         29 . A method for inducing tolerance to an antigen in a subject, the method comprising administering to the subject a population of cells enriched for STRO-1 +  cells and/or progeny thereof and/or soluble factors derived therefrom. 
     
     
         30 . The method of any one of  claims 22  to  29 , wherein the antigen or the specific antigen is one against which an inflammatory response is raised. 
     
     
         31 . The method of  claim 30 , wherein the inflammatory response is causative of an inflammatory neurological disease. 
     
     
         32 . The method of any one of  claims 1  to  31 , wherein the population of cells enriched for STRO-1 +  cells and/or progeny thereof and/or soluble factors derived therefrom is administered with a compound that treats or prevents an inflammatory neurological disease. 
     
     
         33 . The method of  claim 32 , wherein the compound is glatiramer acetate and/or beta-interferon. 
     
     
         34 . A population of cells enriched for STRO-1 +  cells and/or progeny thereof and/or soluble factors derived therefrom for use in the treatment or prevention of an inflammatory neurological disease and/or for suppressing an immune response against an antigen and/or for inducing tolerance to an antigen. 
     
     
         35 . Use of a population of cells enriched for STRO-1 +  cells and/or progeny thereof and/or soluble factors derived therefrom in the manufacture of a medicament for treating or preventing an inflammatory neurological disease and/or for suppressing an immune response against an antigen and/or for inducing tolerance to an antigen.