Sigma ligands for neuronal regeneration and functional recovery

Abstract

The invention discloses methods and compositions useful for facilitating neuronal regeneration and functional recovery in neurodegenerative diseases. The methods and compositions utilize ligands for the sigma receptor, wherein the ligand is preferably SA-4503, or salts, or solvates thereof. These molecules can be delivered alone or in combination with agents which treat or prevent neurodegenerative diseases such as those caused by ischemic stroke, diabetic peripheral neuropathy, cancer therapy induced neuropathy, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, spinal cord injury, Huntington's disease or Parkinson's disease. In other methods, the sigma receptor ligands are administered after stroke to facilitate functional recovery. The administration of the sigma receptor ligands effects faster functional recovery.

1 . A method of treating a mammalian subject to facilitate neuronal regeneration after onset of a neurodegenerative disease, which comprises administering to the subject an effective amount of SA-4503, or salts or solvates thereof. 
     
     
         2 . The method as claimed in  claim 1 , which further comprises assessing the subject for evidence of neuronal regeneration. 
     
     
         3 . The method as claimed in  claim 2 , wherein the evidence of neuronal regeneration is functional recovery in the subject. 
     
     
         4 . The method as claimed in  claim 3 , wherein the functional recovery is recovery in a motor skill, cognitive skill, speech, sensory perception or sensory function. 
     
     
         5 . The method as claimed in  claim 4 , wherein the functional recovery is recovery in a motor skill. 
     
     
         6 . The method as claimed in  claim 4 , wherein the functional recovery is recovery in a cognitive skill. 
     
     
         7 . The method as claimed in  claim 2 , wherein the evidence of neuronal regeneration is a structural change in the brain or spinal cord of the subject. 
     
     
         8 . The method as claimed in  claim 2 , wherein SA-4503 is administered repeatedly to the subject until evidence of neuronal regeneration is found. 
     
     
         9 . The method as claimed in  claim 8 , wherein SA-4503 is administered daily. 
     
     
         10 . The method as claimed in  claim 1 , wherein the neurodegenerative disease is selected from ischemic stroke, traumatic brain injury and spinal cord injury. 
     
     
         11 . The method as claimed in  claim 10 , wherein the treatment is started at least 24 hours after the ischemic stroke, traumatic brain injury or spinal cord injury. 
     
     
         12 . The method as claimed in  claim 10 , wherein the treatment is started at least 48 hours after the ischemic stroke, traumatic brain injury or spinal cord injury. 
     
     
         13 . The method as claimed in  claim 1 , which further comprises exposing the subject to a stimulating environment. 
     
     
         14 . The method as claimed in  claim 1 , wherein the mammalian subject is a human. 
     
     
         15 . A pharmaceutical composition, which comprises SA-4503, or salts or solvates thereof, for treating a mammalian subject to facilitate neuronal regeneration after onset of a neurodegenerative disease, and a pharmaceutically acceptable excipient. 
     
     
         16 . The pharmaceutical composition as claimed in  claim 15 , which further comprises assessing the subject for evidence of neuronal regeneration. 
     
     
         17 . The pharmaceutical composition as claimed in  claim 16 , wherein the neuronal regeneration is evidenced by functional recovery. 
     
     
         18 . The pharmaceutical composition as claimed in  claim 17 , wherein the functional recovery is recovery in a motor skill, cognitive skill, speech, sensory perception or sensory function. 
     
     
         19 . The pharmaceutical composition as claimed in  claim 18 , wherein the functional recovery is recovery in a motor skill. 
     
     
         20 . The pharmaceutical composition as claimed in  claim 18 , wherein the functional recovery is recovery in a cognitive skill. 
     
     
         21 . The pharmaceutical composition as claimed in  claim 16 , wherein the neuronal regeneration is evidenced by a structural change in the brain or spinal cord of the subject. 
     
     
         22 . The pharmaceutical composition as claimed in  claim 15 , wherein SA-4503 is administered repeatedly to the subject until evidence of neuronal regeneration is found. 
     
     
         23 . The A pharmaceutical composition as claimed in  claim 22 , wherein SA-4503 is administered daily. 
     
     
         24 . The pharmaceutical composition as claimed in  claim 15 , wherein the neurodegenerative disease is selected from ischemic stroke, traumatic brain injury and spinal cord injury. 
     
     
         25 . The pharmaceutical composition as claimed in  claim 24 , wherein the treatment is started at least 24 hours after the ischemic stroke, traumatic brain injury or spinal cord injury. 
     
     
         26 . The pharmaceutical composition as claimed in  claim 24 , wherein the treatment is started at least 48 hours after the ischemic stroke, traumatic brain injury or spinal cord injury. 
     
     
         27 . The pharmaceutical composition as claimed in  claim 15 , which further comprises exposing the subject to a stimulating environment. 
     
     
         28 . The pharmaceutical composition as claimed in  claim 15 , wherein the mammalian subject is a human. 
     
     
         29 . A method for facilitating functional recovery after onset of a neurodegenerative disease in a mammalian subject in need thereof, the method comprising:
 administering a pharmaceutically effective amount of SA-4503, or salts or solvates thereof, to the subject.   
     
     
         30 . The method of  claim 29 , which further comprises exposing the subject to a stimulating environment. 
     
     
         31 . The method of  claim 30 , wherein the neurodegenerative disease is selected from the group consisting of ischemic stroke, diabetic peripheral neuropathy, and spinal cord injury. 
     
     
         32 . The method of  claim 31 , wherein the neurodegenerative disease is ischemic stroke. 
     
     
         33 . The method of  claim 31 , wherein the ligand is administered during or immediately after a stroke. 
     
     
         34 . The method of  claim 31 , wherein SA-4503 is administered within 24 hours of the disease onset. 
     
     
         35 . The method of  claim 31 , wherein SA-4503 is administered within 48 hours of the disease onset. 
     
     
         36 . The method of  claim 31 , wherein SA-4503 is administered for at least 2 weeks. 
     
     
         37 . The method of  claim 31 , wherein SA-4503 is administered for 1 month. 
     
     
         38 . The method of  claim 31 , wherein SA-4503 is administered for 3 months. 
     
     
         39 . The method of  claim 31 , wherein SA-4503 is administered for 3 months or longer. 
     
     
         40 . The method of  claim 31 , wherein SA-4503 is administered continuously. 
     
     
         41 . The method of  claim 31 , wherein the subject is human.