ACTIVE SOLUBLE POST-TRANSLATIONALLY MODIFIED NEUREGULIN ISOFORMS
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-1β isoform, a Neuregulin-1α isoform or a SMDF isoform.
5 . The use of claim 4 , wherein the Neuregulin-1 isoform is a Neuregulin-1β 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 (pI) 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.