Use of roluperidone to treat negative symptoms and disorders, increase neuroplasticity, and promote neuroprotection

Abstract

The present application relates to the use of roluperidone, i.e., Compound (I):and salts, solvates, pharmaceutical compositions, and dosage forms thereof, for use in methods of treating negative symptoms and disorders (e.g., autism disorders, amblyopia, personality disorders, traumatic brain injury), as well as increasing neuroplasticity and promoting neuroprotection in subjects in need thereof.

1 . A method of treating or diminishing at least one negative symptom in a subject, comprising administering a therapeutically effective amount of Compound (I), 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or hydrate thereof, to the subject. 
     
     
         2 . The method of  claim 1 , wherein the administration of Compound (I) starts before the manifestation of a first positive symptom in the subject. 
     
     
         3 . The method of  claim 1 , wherein the administration of Compound (I) starts concurrently with the manifestation of a first positive symptom in the subject. 
     
     
         4 . The method of  claim 2 , wherein the positive symptom is a hallucination, delusion, disorganized thinking, movement disorder, or depersonalization. 
     
     
         5 . The method of  claim 1 , wherein the negative symptom is anhedonia, blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficultly in abstract thinking, lack of spontaneity or flow of conversation, or stereotyped thinking. 
     
     
         6 . The method of  claim 1 , wherein the subject is schizophrenic. 
     
     
         7 . The method of  claim 1 , wherein the subject is non-schizophrenic. 
     
     
         8 . The method  claim 1 , wherein the subject suffers from a disorder selected from the group consisting of amblyopia, autism disorder, mental retardation, organic personality disorder, antisocial personality disorder, schizoaffective disorder, schizophreniform disorder, schizoid personality disorder, post-traumatic stress disorder, schizotypal personality disorder, paranoid personality disorder, histrionic personality disorder, narcissistic personality disorder, dependent personality disorder, avoidant personality disorder, somatoform disorder, obsessive compulsive disorder, generalized anxiety disorder, social anxiety disorder, separation anxiety disorder, reactive attachment disorder, panic disorder, depersonalization disorder, derealization disorder, phobia, adjustment disorder, affective disorder, premenstrual dysphoric disorder, selective mutism, obsessive compulsive personality disorder, traumatic brain injury, (neuroleptic-induced) deficit syndrome, arachnoid cysts, bipolar disorder, catalepsy, encephalitis, Huntington's disease, infections (e.g. meningitis), locked-in syndrome, migraines, multiple sclerosis, myelopathy, and Tourette's syndrome. 
     
     
         9 .- 11 . (canceled) 
     
     
         12 . The method of  claim 1 , wherein the administration of Compound (I) increases neuroplasticity in the subject compared with a subject not administered Compound (I), or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
         13 . The method of  claim 1 , wherein the administration of Compound (I) promotes neuroprotection or neural regeneration in the subject compared with a subject not administered Compound (I), or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
         14 .- 18 . (canceled) 
     
     
         19 . A method of increasing neuroplasticity in a subject in need thereof, comprising administering an effective amount of Compound (I), 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or hydrate thereof, to the subject. 
     
     
         20 . The method of  claim 19 , wherein the subject is schizophrenic. 
     
     
         21 . The method of  claim 19 , wherein the subject is non-schizophrenic 
     
     
         22 . The method of  claim 19 , wherein the subject suffers from a disorder selected from the group consisting of amblyopia, autism disorder, mental retardation, organic personality disorder, antisocial personality disorder, schizoaffective disorder, schizophreniform disorder, schizoid personality disorder, post-traumatic stress disorder, schizotypal personality disorder, paranoid personality disorder, histrionic personality disorder, narcissistic personality disorder, dependent personality disorder, avoidant personality disorder, somatoform disorder, obsessive compulsive disorder, generalized anxiety disorder, social anxiety disorder, separation anxiety disorder, reactive attachment disorder, panic disorder, depersonalization disorder, derealization disorder, phobia, adjustment disorder, affective disorder, premenstrual dysphoric disorder, selective mutism, obsessive compulsive personality disorder, traumatic brain injury, (neuroleptic-induced) deficit syndrome, arachnoid cysts, bipolar disorder, catalepsy, encephalitis, Huntington's disease, infections (e.g. meningitis), locked-in syndrome, migraines, multiple sclerosis, myelopathy, and Tourette's syndrome. 
     
     
         23 . A method of promoting neuroprotection in a subject in need thereof, the method comprising contacting a neuronal cell with an effective amount of Compound (I), 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or hydrate thereof, wherein said contacting prevents or delays neuronal cell death relative to neuronal cell death occurring in the absence of said contacting, or wherein said contacting promotes nerve regeneration by stimulating neuronal growth. 
     
     
         24 . The method of  claim 23 , wherein the subject is schizophrenic. 
     
     
         25 . The method of  claim 23 , wherein the subject is non-schizophrenic. 
     
     
         26 . The method of  claim 23 , wherein the subject suffers from a disorder selected from the group consisting of amblyopia, autism disorder, mental retardation, organic personality disorder, antisocial personality disorder, schizoaffective disorder, schizophreniform disorder, schizoid personality disorder, post-traumatic stress disorder, schizotypal personality disorder, paranoid personality disorder, histrionic personality disorder, narcissistic personality disorder, dependent personality disorder, avoidant personality disorder, somatoform disorder, obsessive compulsive disorder, generalized anxiety disorder, social anxiety disorder, separation anxiety disorder, reactive attachment disorder, panic disorder, depersonalization disorder, derealization disorder, phobia, adjustment disorder, affective disorder, premenstrual dysphoric disorder, selective mutism, obsessive compulsive personality disorder, traumatic brain injury, (neuroleptic-induced) deficit syndrome, arachnoid cysts, bipolar disorder, catalepsy, encephalitis, Huntington's disease, infections (e.g. meningitis), locked-in syndrome, migraines, multiple sclerosis, myelopathy, and Tourette's syndrome. 
     
     
         27 . A method of increasing brain-derived neurotropic factor (BDNF) expression in a cell, comprising contacting the cell with an effective amount of Compound (I), 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
         28 .- 29 . (canceled) 
     
     
         30 . A method of increasing glial cell line-derived neurotrophic factor (GDNF) expression in a cell, comprising contacting the cell with an effective amount of Compound (I), 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
         31 .- 32 . (canceled)