IgG STIMULATED REMYELINATION OF PERIPHERAL NERVES

Abstract

The present invention is based on the discovery of polyclonal IgG's ability to promote Schwann cell maturation, differentiation, and myelin production. Methods for treating non-idiopathic, demyelinating peripheral neuropathies in mammals, where the neuropathy is not immune-mediated or infection-mediated, through the administration of polyclonal IgG are provided. Types of demyelinating peripheral neuropathies treatable with the present invention include peripheral nerve trauma and toxin-induced peripheral neuropathies. Alternatively, a composition of polyclonal IgGs can be applied directly to a peripheral nerve cell to induce maturation, differentiation into a myelinating state, and myelin expression or promote cell survival.

What is claimed is: 
     
         1 . A method of treating a demyelinating peripheral neuropathy comprising administering a therapeutically effective amount of polyclonal IgG to a mammal diagnosed with said neuropathy, with the proviso that said neuropathy is not an immune-mediated or infection-mediated neuropathy and excludes Guillain-Barré syndrome, chronic demyelinating polyneuropathy and multifocal motor neuropathy. 
     
     
         2 . The method of  claim 1 , wherein the mammal is human. 
     
     
         3 . The method of any of  claims 1 - 2 , wherein the polyclonal IgG is administered locally. 
     
     
         4 . The method of  claim 3 , wherein the polyclonal IgG is administered intramuscularly or intradermally. 
     
     
         5 . The method of any of  claims 1 - 2 , wherein the polyclonal IgG is administered systemically. 
     
     
         6 . The method of  claim 5 , wherein the polyclonal IgG is administered intranasally, subcutaneously, orally, intra-arterially or intravenously. 
     
     
         7 . The method of any of  claims 1 - 6 , wherein an anti-inflammatory agent is co-administered with the polyclonal IgG to the mammal. 
     
     
         8 . The method of  claim 7 , wherein the anti-inflammatory agent is adrenocorticotropic hormone, a corticosteroid, an interferon, glatiramer acetate, or a non-steroidal anti-inflammatory drug. 
     
     
         9 . The method of any of  claims 1 - 8 , wherein the demyelinating peripheral neuropathy is selected from a trauma-induced neuropathy, a toxin-induced neuropathy, an inherited neuropathy, and a neuropathy induced by a metabolic disease. 
     
     
         10 . The method of  claim 9 , wherein the peripheral neuropathy is a trauma-induced neuropathy. 
     
     
         11 . The method of  claim 9 , wherein the peripheral neuropathy is a toxin-induced neuropathy. 
     
     
         12 . The method of  claim 9 , wherein the peripheral neuropathy is an inherited neuropathy. 
     
     
         13 . The method of  claim 9 , wherein the peripheral neuropathy is induced by a metabolic disease. 
     
     
         14 . The method of  claim 13 , wherein the peripheral neuropathy is diabetic neuropathy. 
     
     
         15 . The method of any of  claims 1 - 8 , wherein the demyelinating peripheral neuropathy is motor neuropathy. 
     
     
         16 . The method of any of  claims 1 - 8 , wherein the demyelinating peripheral neuropathy is sensory neuropathy. 
     
     
         17 . The method of any of  claims 1 - 8 , wherein the demyelinating peripheral neuropathy is sensorimotor neuropathy. 
     
     
         18 . The method of any of  claims 1 - 8 , wherein the demyelinating peripheral neuropathy is autonomic neuron neuropathy. 
     
     
         19 . The method of any of  claims 1 - 18 , wherein the polyclonal IgG is administered weekly. 
     
     
         20 . The method of any of  claims 1 - 18 , wherein the polyclonal IgG is administered biweekly. 
     
     
         21 . The method of any of  claims 1 - 18 , wherein the polyclonal IgG is administered monthly. 
     
     
         22 . The method of any of  claims 1 - 21 , wherein the polyclonal IgG is administered to the mammal at a dose of about 0.05 to 5 g per kg of patient body weight. 
     
     
         23 . The method of  claim 22 , wherein the polyclonal IgG is administered to the mammal at a dose of about 0.5 to 2 g per kg of patient body weight. 
     
     
         24 . A method of treating peripheral nerve trauma comprising administering a therapeutically effective amount of polyclonal IgG to a mammal with peripheral nerve trauma. 
     
     
         25 . The method of  claim 24 , wherein the polyclonal IgG is administered locally. 
     
     
         26 . The method of  claim 23 , wherein the polyclonal IgG is administered intramuscularly or intradermally. 
     
     
         27 . The method of  claim 24 , wherein the polyclonal IgG is administered systemically. 
     
     
         28 . The method of  claim 27 , wherein the polyclonal IgG is administered intranasally, orally, intra-arterially, subcutaneously, or intravenously. 
     
     
         29 . The method of any of  claims 24 - 28 , wherein the polyclonal IgG is administered to the mammal at a dose of about 0.05 to 5 g per kg of patient body weight. 
     
     
         30 . The method of  claim 29 , wherein the polyclonal IgG is administered to the mammal at a dose of about 0.5 to 2 g per kg of patient body weight. 
     
     
         31 . The method of any of  claims 24 - 30 , wherein an anti-inflammatory agent is co-administered with the polyclonal IgG to the mammal. 
     
     
         32 . The method of  claim 31 , wherein the anti-inflammatory agent is adrenocorticotropic hormone, a corticosteroid, an interferon, glatiramer acetate, or a non-steroidal anti-inflammatory drug. 
     
     
         33 . The method of any of  claims 24 - 32 , wherein the mammal is human. 
     
     
         34 . A method of treating toxin-induced peripheral neuropathy comprising administering a therapeutically effective amount of polyclonal IgG to a mammal diagnosed with said neuropathy, wherein said neuropathy is not infection-mediated. 
     
     
         35 . The method of  claim 34 , wherein the polyclonal IgG is administered locally. 
     
     
         36 . The method of  claim 35 , wherein the polyclonal IgG is administered intramuscularly or intradermally. 
     
     
         37 . The method of  claim 34 , wherein the polyclonal IgG is administered systemically. 
     
     
         38 . The method of  claim 37 , wherein the polyclonal IgG is administered intranasally, orally, intra-arterially, subcutaneously, or intravenously. 
     
     
         39 . The method of any of  claims 34 - 38 , wherein the polyclonal IgG is administered to the mammal at a dose of about 0.05 to 5 g per kg of patient body weight. 
     
     
         40 . The method of  claim 39 , wherein the polyclonal IgG is administered to the mammal at a dose of about 0.5 to 2 g per kg of patient body weight. 
     
     
         41 . The method of any of  claims 34 - 40 , wherein an anti-inflammatory agent is co-administered with the polyclonal IgG to the mammal. 
     
     
         42 . The method of  claim 41 , wherein the anti-inflammatory agent is adrenocorticotropic hormone, a corticosteroid, an interferon, glatiramer acetate, or a non-steroidal anti-inflammatory drug. 
     
     
         43 . The method of any of  claims 34 - 42 , wherein the mammal is human. 
     
     
         44 . A method of promoting myelination of a peripheral nerve cell by a Schwann cell comprising contacting said Schwann cell with an amount of polyclonal IgG sufficient to promote myelination of said peripheral nerve cell by the Schwann cell. 
     
     
         45 . A method of promoting the differentiation of an immature Schwann cell into a myelinating state comprising contacting said Schwann cell with polyclonal IgG in an amount sufficient to induce the Schwann cell differentiation. 
     
     
         46 . A method of promoting the production of myelin by a Schwann cell comprising contacting said Schwann cell with an amount of polyclonal IgG sufficient to upregulate MBP genes. 
     
     
         47 . A method of culturing mammalian nervous tissue which comprises axons, said method comprising contacting the tissue in culture with an effective amount of Schwann cells and an effective amount of polyclonal IgG, whereby the contacting of Schwann cells with polyclonal IgG induces upregulation of MBP genes. 
     
     
         48 . A method of treating a peripheral nerve injury in a mammal comprising:
 transplanting nerve cells to a site of the peripheral nerve injury;   contacting the nerve cells with a composition comprising Schwann cells and polyclonal IgG.   
     
     
         49 . The method of  claim 48 , wherein the mammal is human.