Treatment of bdnf-related disorders using laquinimod

Abstract

This application provides for a method of increasing brain-derived neurotrophic factor (BDNF) serum level in a human subject comprising periodically administering to the subject an amount of laquinimod or pharmaceutically acceptable salt thereof effective to increase BDNF serum level in the human subject. The method can further comprise periodically administering to the subject an amount of a second BDNF-increasing agent. This application also provides for a method for treating a human subject suffering from a BDNF-related disease comprising periodically administering laquinimod or a pharmaceutically acceptable salt thereof in an amount effective to treat the human subject. This application additionally provides for use of laquinimod in the manufacture of a medicament for increasing BDNF serum level in a human subject. This application further provides for a pharmaceutical composition comprising an amount of laquinimod effective for use in increasing BDNF serum level in a human subject. This application also provides for a pharmaceutical preparation comprising an amount of laquinimod and an amount of a second BDNF-increasing agent effective for use in increasing BDNF serum level in a human subject.

What is claimed is: 
     
         1 . A method of increasing brain-derived neurotrophic factor (BDNF) serum level in a human subject comprising periodically administering to the subject an amount of laquinimod or pharmaceutically acceptable salt thereof effective to increase BDNF serum level in the human subject. 
     
     
         2 . The method of  claim 1 , wherein the amount of laquinimod or pharmaceutically acceptable salt thereof is administered to the human subject once daily. 
     
     
         3 . The method of  claims 1  or  2 , wherein the periodic administration continues for at least 3 days. 
     
     
         4 . The method of any one of  claims 1 - 3 , wherein the amount of laquinimod administered is 0.1 mg/day-40.0 mg/day. 
     
     
         5 . The method of  claim 4 , wherein the amount of laquinimod administered is 0.6 mg/day. 
     
     
         6 . The method of any one of  claims 1 - 5 , wherein the amount of laquinimod is administered orally. 
     
     
         7 . The method of any one of  claims 1 - 6 , wherein the subject is suffering from a BDNF-related disease. 
     
     
         8 . The method of  claim 7 , wherein the BDNF-related disease is Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, a depressive disorder, an anxiety disorder, retinitis pigmentosa, erectile dysfunction, a memory disorder, Rett syndrome, Alzheimer's disease, bipolar disorder or acute mania. 
     
     
         9 . The method of  claim 8 , wherein the depressive disorder is depression, depression in cancer patients, depression in Parkinson's disease patients, postmyocardia infarction depression, depression in patients with human immunodeficiency virus (HIV), subsyndromal symptomatic depression, depression in infertile women, pediatric depression, major depression, single episode depression, recurrent depression, child abused-induced depression, post-partum depression, DSM-IV major depression, treatment-refractory major depression, severe depression, psychotic depression, post-stroke depression, neuropathic pain, manic depressive illness including manic depressive illness with mixed episodes and manic depressive illness with depressive episodes, seasonal affective disorder, bipolar depression BP I, bipolar depression BP II, or major depression with dysthymia. 
     
     
         10 . The method of  claim 8 , wherein the anxiety disorder is generalized anxiety, panic disorder, phobia, post traumatic stress disorder, obsessive compulsive disorder, separation anxiety, or childhood anxiety. 
     
     
         11 . The method of any one of  claims 1 - 10 , the method further comprising periodically administering to the subject an amount of a second BDNF-increasing agent. 
     
     
         12 . The method of  claim 11 , wherein the amount of the second BDNF-increasing agent when taken alone is not effective to increase BDNF serum level in the subject. 
     
     
         13 . The method of  claims 11  or  12 , wherein the administration of the laquinimod substantially precedes the administration of the second BDNF-increasing agent. 
     
     
         14 . The method of  claims 11  or  12 , wherein the administration of the second BDNF-increasing agent substantially precedes the administration of the laquinimod. 
     
     
         15 . The method of any one of  claims 11 - 14 , wherein the effect on the subject is greater than the effect on a subject treated with the second BDNF-increasing agent alone. 
     
     
         16 . The method of  claim 15 , wherein the increase in BDNF serum level in the subject is greater than the increase in BDNF serum level in a subject treated with the second BDNF-increasing agent alone. 
     
     
         17 . The method of any one of  claims 1 - 16 , wherein the pharmaceutically acceptable salt of laquinimod is laquinimod sodium. 
     
     
         18 - 21 . (canceled)