Cyclic peptidomimetic for the treatment of neurological disorders

Abstract

The present invention provides to compositions and methods useful in the treatment of neurological disorders including, but not limited to, Angelman syndrome, depression, traumatic brain injury, stroke, and Alzheimer's disease. CN2097, a rationally designed cyclic peptidomimetic drug that has been demonstrated to have effectiveness in preclinical models for the treatment of neurological disorders, is rapidly cleared and has a short half-life. The present invention provides a stable analog of CN2097.

1 . An analog of CN-2097 (“(Arg) 7 ” is disclosed as SEQ ID NO: 4 below) 
       
         
           
           
               
               
           
         
       
       said analog represented by dR 7 -2097 wherein the analog essentially consists of dextrorotatory (D)-amino acids (dR 7 -NH 2 ). 
     
     
         2 . A pharmaceutical composition comprising a therapeutically-effective amount of the analog of CN-2097, dR 7 -2097, or a pharmaceutically-acceptable salt thereof, and one or more pharmaceutically-acceptable carrier. 
     
     
         3 . A method of preventing or treating a neurological disorder in a subject at risk of or afflicted with the neurological disorder comprising administering a composition comprising (a) a therapeutically-effective amount of the analog of CN-2097, dR 7 -2097, and (b) at least one pharmaceutically-acceptable carrier. 
     
     
         4 . The method of  claim 3 , wherein the neurological disorder is depression. 
     
     
         5 . The method of  claim 4 , wherein the depression is treatment-resistant depression. 
     
     
         6 . The method of  claim 4 , wherein the depression is selected from the group consisting of: major depressive disorder, dysthymic disorder, psychotic depression, postpartum depression, seasonal affective disorder, bipolar disorder, bipolar depression, mood disorder, depressions caused by chronic medical conditions such as cancer or chronic pain, chemotherapy, chronic stress, post-traumatic stress disorders, and manic depressive disorder. 
     
     
         7 . The method of  claim 3 , wherein the neurological disorder is selected from the group consisting of: Angelman syndrome, traumatic brain injury, spinal cord injury, glaucoma, stroke, cerebrovascular accident (CVA), and Alzheimer's disease.