Method of effecting neuroprotection using soluble 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 . A method of treating a subject suffering from Alzheimer's disease, comprising administering to said subject a recombinant soluble Type I Neuregulin-1 β isoform which is an about 15 to about 35 kD N-terminal fragment of Type I Neuregulin-1β, wherein said recombinant soluble Type I Neuregulin-1 β isoform is the first 245, 246, 247, 248, 249, or 250 amino acids of Type I Neuregulin-1 
     
     
         2 . The method of  claim 1 , wherein said recombinant soluble Type I Neuregulin-1 β isoform is the first 245 amino acids of Type I Neuregulin-1β. 
     
     
         3 . The method of  claim 1 , wherein said recombinant soluble Type I Neuregulin-1 β isoform crosses the blood-brain barrier. 
     
     
         4 . The method of  claim 1 , wherein said recombinant soluble Type I Neuregulin-1 β isoform reduces dopaminergic cell death in said subject compared to a subject that is not treated with said recombinant soluble Type I Neuregulin-1 β isoform. 
     
     
         5 . The method of  claim 1 , wherein the Type I Neuregulin-1 β isoform has an isoelectric point (p1) of about 4 to about 10. 
     
     
         6 . The method of  claim 1 , wherein the Type I Neuregulin-1 β isoform is a modified polypeptide, wherein the modifications are selected from phosphorylation, glycosylation, methylation, myristoylation, oxidation and any combination thereof. 
     
     
         7 . The method of  claim 1 , wherein said recombinant soluble Type I Neuregulin-1 β isoform is administered in an amount of 3 to 600 ng/kg body weight of the subject to be treated. 
     
     
         8 . The method of  claim 1 , wherein said recombinant soluble Type I Neuregulin-1 β isoform is administered in an amount of 150 to 300 ng/kg body weight of the subject to be treated. 
     
     
         9 . The method of  claim 1 , wherein said recombinant soluble Type I Neuregulin-1 β isoform is administered in an amount of about 3, 5, 20, 50, 150, 200, 300 or 600 ng/kg body weight of the subject to be treated. 
     
     
         10 . The method of  claim 1 , wherein said recombinant soluble Type I Neuregulin-1 β isoform is administered in an amount of about 20 ng/kg body weight of the subject to be treated. 
     
     
         11 . The method of  claim 1 , wherein the administration is by intravenous or intraperitoneal injection.