Active soluble post-translationally modified neuregulin isoforms

Abstract

The present invention refers to soluble Neuregulin-1 isoforms representing Posttranslational Neuregulin-1 modifications as medication in cognition-related neurological disorders, in particular schizophrenia, Alzheimer's and Parkinson's diseases.

1 . Use of a recombinant soluble Neuregulin-1 isoform for the manufacture of a medicament for the treatment of neurological conditions. 
     
     
         2 . The use of  claim 1  for the treatment of schizophrenia, in particular cognition-related aspects of schizophrenia, bipolar disorder and depression, Parkinson's disease, Alzheimer's disease, epilepsy, MS, ALS, stroke, traumatic brain injury and spinal chord injury. 
     
     
         3 . The use of  claim 1 , wherein the Neuregulin-1 isoform is a recombinant soluble human Neuregulin-1 isoform. 
     
     
         4 . The use of  claim 1 , wherein the Neuregulin-1 isoform is a Neuregulin-1 β isoform, a Neuregulin-1 α isoform or a SMDF isoform. 
     
     
         5 . The use of  claim 4 , wherein the Neuregulin-1 isoform is a Neuregulin-1 β isoform. 
     
     
         6 . The use of  claim 1 , wherein the Neuregulin-1 isoform comprises at least a portion of the extracellular domain. 
     
     
         7 . The use of  claim 1 , wherein the Neuregulin-1 isoform has a molecular weight of about 15 to about 35 KD as measured by SDS-PAGE. 
     
     
         8 . The use of  claim 1 , wherein the Neuregulin-1 isoform has an isoelectric point (pl) of about 4 to about 10, preferably of about 4 to about 6. 
     
     
         9 . The use of  claim 1 , wherein the Neuregulin-1 isoform is a modified polypeptide, wherein the modifications are selected from phosphorylation, glycosylation, methylation, myristylation, oxidation and any combination thereof. 
     
     
         10 . The use of  claim 1  in combination with a further medicament. 
     
     
         11 . The use of  claim 10 , wherein the further medicament is a medicament for the treatment of neurological conditions. 
     
     
         12 . The use of  claim 11 , wherein the further medicament is selected from compounds affecting catecholamine metabolism, acetylcholine esterase inhibitors, MAO-B- or COMT-inhibitors, Memantine-type channel blockers, dopamine or serotonine receptor agonists or antogonists, catecholamine or serotonine reuptake inhibitors or any type of antipsychotic medication like clozapine or olanzapine or gabapentin-like drugs in the treatments of Alzheimer's and Parkinson's diseases, schizophrenia, bipolar disorder, depression or other neurological conditions. 
     
     
         13 . The use of  claim 10 , wherein the further medicament is a medicament for the treatment of psychotic disorders such as schizophrenia, bipolar disorders and depression, e.g. olanzapine or clozapine. 
     
     
         14 . The use of  claim 10 , wherein the further medicament is a medicament for the treatment of Parkinson's disease. 
     
     
         15 . The use of  claim 10 , wherein the further medicament is a medicament for the treatment of Alzheimer's disease. 
     
     
         16 . The use of  claim 10 , wherein the further medicament is a medicament for the treatment of Multiple Sclerosis (MS). 
     
     
         17 . The use of  claim 10 , wherein the further medicament is a medicament for the treatment of Amylotrophic Lateral Sclerosis (ALS). 
     
     
         18 . The use of  claim 10 , wherein the further medicament is a medicament for the treatment of epilepsy. 
     
     
         19 . The use of  claim 10 , wherein the further medicament is a medicament for the treatment of stroke. 
     
     
         20 . The use of  claim 10 , wherein the further medicament is a medicament for the treatment of traumatic brain injury. 
     
     
         21 . The use of  claim 10 , wherein the further medicament is a medicament for the treatment of spinal chord injury. 
     
     
         22 . A pharmaceutical composition or kit comprising:
 (i) a recombinant soluble Neuregulin-1 isoform and   (ii) a further medicament particularly for the treatment of neurological conditions.   
     
     
         23 . Use of a recombinant soluble Neuregulin-1 isoform for the manufacture of a medicament for memory and cognition enhancement. 
     
     
         24 . The use of  claim 21  for reducing and/or inhibiting memory and cognition loss associated with a neurological condition such as Alzheimer's disease. 
     
     
         25 . (canceled) 
     
     
         26 . A method of treating a neurological condition, comprising administering a recombinant soluble Neuregulin-1 isoform in a pharmaceutically effective amount to a subject in need thereof. 
     
     
         27 . A method for enhancing memory and cognition, comprising administering a recombinant soluble Neuregulin-1 isoform in a pharmaceutically effective amount to a subject in need thereof.