Cell Membrane Translocation of Regulated Snare Inhibitors, Compositions Therefor, and Methods for Treatment of Disease

Abstract

Compositions and methods of modulating cellular function and treatment of disease in mammals comprising locally administering a regulated SNARE inhibitor and a translocating agent to the mammal. Regulated SNARE inhibitors include clostridial neurotoxins, tetanus neurotoxin and their free light chain portions and IgA protease. Translocating agents include acids, encapsulating vectors, and transduction domains.

1 .  116 . (canceled) 
     
     
         117 . A method of treating or reduction of symptoms associated with inflammation in a mammal in need thereof comprising administering a therapeutically effective amount of a botulinum neurotoxin to treat or reduce symptoms associated with inflammation into the mammal's pterygopalatine space, thereby blocking the mammal's sphenopalatine ganglion. 
     
     
         118 . The method of  claim 117 , wherein the botulinum neurotoxin is administered by injection. 
     
     
         119 . The method of  claim 117 , wherein the botulinum neurotoxin is topically administered. 
     
     
         120 . The method of  claim 117 , wherein the botulinum neurotoxin is selected from the group consisting of botulinum neurotoxin serotypes A, B, C1, D, E, F and G. 
     
     
         121 . The method of  claim 119 , wherein the botulinum neurotoxin is botulinum neurotoxin serotype A. 
     
     
         122 . The method of  claim 117 , wherein said administering step comprises the steps of passing a needle about 1.5 inches through the sphenopalatine canal and injecting the botulinum neurotoxin into the mammal's pterygopalatine space. 
     
     
         123 . The method of  claim 117 , wherein said symptoms associated with inflammation includes congestion, primary inflammation and neurogenic inflammation. 
     
     
         124 . The method of  claim 117 , wherein said administration of a therapeutically effective amount of botulinum neurotoxin decreases rhinorrhea, congestion, primary inflammation, neurogenic inflammation, or combinations thereof. 
     
     
         125 . The method of  claim 117 , wherein said administration of a therapeutically effective amount of botulinum neurotoxin inhibits mast cell release of bioactive substances. 
     
     
         126 . The method of  claim 117 , wherein the botulinum neurotoxin is administered at a dosage of between about 0.1 units to about 1000 units. 
     
     
         127 . The method of  claim 117 , wherein the botulinum neurotoxin is administered at a dosage of between about 1 unit to about 100 units. 
     
     
         128 . The method of  claim 117 , wherein the botulinum neurotoxin is administered by way of acid mediated translocation, protein transduction domains, or encapsulation vectors. 
     
     
         129 . A method of treating or reduction of symptoms associated with inflammation in a mammal in need thereof comprising administered a therapeutically effective amount of botulinum neurotoxin serotype A to treat or reduce symptoms associated with inflammation into the mammal's pterygopalatine space, thereby blocking the mammal's sphenopalatine ganglion. 
     
     
         130 . The method of  claim 129 , wherein said symptoms associated with inflammation includes congestion, primary inflammation and neurogenic inflammation. 
     
     
         131 . The method of  claim 129 , wherein said administration of a therapeutically effective amount of botulinum neurotoxin serotype A decreases rhinorrhea, congestion, primary inflammation and neurogenic inflammation. 
     
     
         132 . The method of  claim 129 , wherein said administration of a therapeutically effective amount of botulinum neurotoxin serotype A inhibits mast cell release of bioactive substances. 
     
     
         133 . The method of  claim 129 , wherein said administering step comprises the steps of passing a needle about  1 . 5  inches through the sphenopalatine canal and injecting the botulinum neurotoxin serotype A into the mammal's pterygopalatine space. 
     
     
         134 . The method of  claim 129 , wherein the botulinum neurotoxin serotype A is administered at a dosage of between about 0.1 units to about 1000 units. 
     
     
         135 . The method of  claim 129 , wherein the botulinum neurotoxin serotype A is administered at a dosage of between about 1 unit to about 100 units. 
     
     
         136 . The method of  claim 129 , wherein the botulinum neurotoxin serotype A is administered by way of acid mediated translocation, protein transduction domains, or encapsulation vectors.