Modified ciliary neurotrophic factor, method of making and methods of use thereof

Abstract

Modified ciliary neurotrophic factor, methods for production and methods of use, especially in the treatment of Huntington's disease, obesity, and gestational or adult onset diabetes.

We claim:  
     
         1 . Modified human ciliary neurotrophic factor having the modification Cys17→Ala, Gln63→Arg, and a deletion of the terminal 15 amino acid residues.  
     
     
         2 . An isolated nucleic acid molecule encoding the modified human ciliary neurotrophic factor of  claim 1 .  
     
     
         3 . A recombinant DNA molecule of  claim 2 , operatively linked to an expression control sequence.  
     
     
         4 . A host cell transformed with the recombinant DNA molecule of  claim 3 .  
     
     
         5 . A method for producing a modified ciliary neurotrophic factor molecule comprising: (a) growing a recombinant host cell containing the DNA molecule of  claim 3 , so that the DNA molecule is expressed by the host cell to produce the modified ciliary neurotrophic factor molecule and (b) isolating the expressed, modified ciliary neurotrophic factor molecule.  
     
     
         6 . The method according to  claim 5 , wherein said host cell is a eukaryotic cell.  
     
     
         7 . The method according to  claim 5 , wherein said host cell is a prokaryotic cell.  
     
     
         8 . A composition comprising the modified ciliary neurotrophic factor molecule of  claim 1 , and a carrier.  
     
     
         9 . A method of treating a disease or disorder of the nervous system comprising administering the modified ciliary neurotrophic factor of  claim 1 .  
     
     
         10 . The method according to  claim 9 , wherein said disease or disorder is a degenerative disease.  
     
     
         11 . The method according to  claim 9 , wherein said disease or disorder involves the spinal cord, motor neurons, cholinergic neurons or cells of the hippocampus.  
     
     
         12 . The method according to  claim 9 , in which the disease or disorder of the nervous system comprises damage to the nervous system caused by an event selected from the group consisting of trauma, surgery, infarction, infection, malignancy and exposure to a toxic agent.  
     
     
         13 . The method according to  claim 9 , wherein said disease or disorder involves muscle atrophy.  
     
     
         14 . A method of protecting striatal neurons from degeneration comprising treating said striatal neurons with an effective amount of the modified ciliary neurotrophic factor of  claim 1 .  
     
     
         15 . A method of treating Huntington's disease comprising direct administration to the central nervous system of the modified ciliary neurotrophic factor of  claim 1 .  
     
     
         16 . A method of inducing weight loss in a mammal comprising administration of the modified ciliary neurotrophic factor of  claim 1 .  
     
     
         17 . The method of  claim 16 , wherein the mammal is a human.  
     
     
         18 . The method  claim 17 , used in the treatment of morbid obesity or obesity of a genetically determined origin.  
     
     
         19 . A method of preventing the occurrence of gestational or adult onset diabetes in a human comprising administration of the modified ciliary neurotrophic factor of  claim 1 .  
     
     
         20 . A method of treating gestational or adult onset diabetes in a human comprising administration of the modified ciliary neurotrophic factor of  claim 1 .  
     
     
         21 . The method according to any one of  claims 15  to  20 , wherein said administration is via a route of delivery selected from the group consisting of intravenous, subcutaneous, intramuscular, intrathecal, intracerebroventricular and intraparenchymal.  
     
     
         22 . The method according to any one of  claims 15  to  20 , wherein said administration is via implantation of cells that release the modified ciliary neurotrophic factor.