Method of effecting neuroprotection using soluble neuregulin isoforms

Abstract

Soluble Neuregulin-1 isoforms representing Posttranslational Neuregulin-1 modifications as medication for effecting neuroprotection in a subject suffering from schizophrenia, bipolar disorder, depression, Alzheimer's disease, epilepsy, multiple sclerosis (MS), Amylotrophic Lateral Sclerosis (ALS), stroke, traumatic brain injury, and/or spinal cord injury.

1 . A method of effecting neuroprotection in a subject suffering from a condition selected from the group consisting of schizophrenia, bipolar disorder, depression, Alzheimer's disease, epilepsy, multiple sclerosis (MS), Amylotrophic Lateral Sclerosis (ALS), stroke, traumatic brain injury, and spinal cord injury, 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. 
     
     
         2 . The method of  claim 1 , wherein said recombinant soluble Type I Neuregulin-1 β isoform is the first 150 to 250 amino acids of Type I Neuregulin-1 β. 
     
     
         3 . The method of  claim 1 , wherein said recombinant soluble Type I Neuregulin-1 β isoform is the first 245 to 250 amino acids of Type I Neuregulin-1 β. 
     
     
         4 . The method of  claim 1 , wherein said recombinant soluble Type I Neuregulin-1 β isoform crosses the blood-brain barrier. 
     
     
         5 . 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. 
     
     
         6 . The method of  claim 1 , wherein said recombinant soluble Type I Neuregulin-1 β isoform is administered to said patient in combination with a further medicament. 
     
     
         7 . The method of  claim 6 , wherein the further medicament is selected from the group consisting of acetylcholine esterase inhibitors, MAO-B-inhibitors, COMT-inhibitors, Memantine-type channel blockers, dopamine receptor agonists, serotonine receptor agonists or antogonists, catecholamine reuptake inhibitors, serotonine reuptake inhibitors. 
     
     
         8 . The method of  claim 6 , wherein the further medicament is a medicament for the treatment of psychotic disorders such as schizophrenia, bipolar disorders and depression. 
     
     
         9 . The method of  claim 6 , wherein the further medicament is a medicament for the treatment of Alzheimer's disease. 
     
     
         10 . The method of  claim 6 , wherein the further medicament is a medicament for the treatment of Multiple Sclerosis (MS). 
     
     
         11 . The method of  claim 6 , wherein the further medicament is a medicament for the treatment of Amyotrophic Lateral Sclerosis (ALS). 
     
     
         12 . The method of  claim 6 , wherein the further medicament is a medicament for the treatment of epilepsy. 
     
     
         13 . The method of  claim 6 , wherein the further medicament is a medicament for the treatment of stroke. 
     
     
         14 . The method of  claim 6 , wherein the further medicament is a medicament for the treatment of traumatic brain injury. 
     
     
         15 . The method of  claim 6 , wherein the further medicament is a medicament for the treatment of spinal cord injury. 
     
     
         16 . The method of  claim 1 , wherein the Type I Neuregulin-1 β isoform has an isoelectric point (pl) of about 4 to about 10. 
     
     
         17 . 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. 
     
     
         18 . 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. 
     
     
         19 . 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. 
     
     
         20 . 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. 
     
     
         21 . 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.