Use of neuregulin-beta as an indicator and/or target

• US 20030036101A1
• Filed: 08/09/2002
• Published: 02/20/2003
• Est. Priority Date: 02/11/2000
• Status: Active Grant

• Current Assignee: Mind-NRG SA
• Original Assignee: Proteosys AG
• Inventors: Schrattenholz, Andre
• Granted Patent: US 7,538,197 B2
• Time in Patent Office: Days
• US Class Current: 435/7.21
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07K 14/4756 Neuregulins, i.e. p185erbB2 ligands, glial growth factor, heregulin, ARIA, neu differentiation factor

Abstract

The invention relates, inter alia, to the use of neuregulin-β as a target in a screening method for active compounds, in particular for exerting an influence on changes in calcium concentration which are mediated by glutamate receptors.

The invention furthermore relates to the use of neuregulins, preferably a neuregulin isoform having an isoelectric point in the range from pH 4.3 to 5.0, as a target for detecting and/or exerting an influence on neuronal processes, in particular for exerting an influence on long-term memory. Neuregulins, in particular neuregulin-β and also substances which exert an influence on the status, i.e. the expression and/or post-translational modification, of neuregulin-β, can therefore be used as agents for controlling the course of, treating and/or alleviating neuronal diseases, e.g. Alzheimer'"'"'s disease.

Claims

1. A neuregulin-β

isoform having an isoelectric point (pI) in the range of ≦

pH 7.

2. A neuregulin-β

isoform as claimed in claim 1 having a pI in the range from pH 4.3 to 5.0.

3. A neuregulin-β

isoform as claimed in claim 1 or 2 having a pI in the range from pH 4.5 to 4.7.

4. The use of neuregulin-β

as claimed in claim 1, 2 or 3 as an indicator and/or target in a screening method for identifying active compounds.

5. The use of neuregulin-β

as claimed in claim 1, 2 or 3 as an indicator and/or target in a screening method for identifying active compounds for exerting an influence on glutamate receptor-mediated changes in calcium concentration.

6. The use of neuregulin-β

as claimed in claim 1, 2 or 3 as an indicator and/or target in a screening method for identifying active compounds, with the screening method being a method for collecting multidimensional performance data for the effect space/effector space analysis of active compounds,

in which cell culture systems, which have been introduced into a flow cell device and applied to substrates, are incubated with fluorescent dyes which are in each case suitable and/or with isotopic mixtures of different elements,

the cell culture systems are stimulated, and

the fluorescence signals resulting in dependence on the stimulation conditions are detected, directly in the cell culture system, in a chronologically synchronous and time-resolved manner, and/or the isotopic mixtures are detected in the perfusate in a time-resolved manner, and/or the isotopic mixtures are detected directly in the cell culture systems in a time-integrated manner,

with the perfusate being subjected to a synchronized fractionation and continuing analysis,

proteins which are present in the cell culture systems and which change under the chosen conditions and/or behave specifically being characterized and identified, and

the multidimensional performance data which had been obtained for the effect space/effector space analysis of active compounds finally being integrated.

7. The use as claimed in one of claims 4 to 6, characterized in that

neuregulin-β

is used as an indicator and/or target for exerting an influence on neuronal processes such as long-term potentiation (LTP), long-term depression (LTD), epileptiform and/or epileptogenic events and/or excitation-toxic phenomena.

8. The use as claimed in one of claims 4 to 6, characterized in that

neuregulin-β

is used as an indicator and/or target for exerting an influence on neuronal diseases, in particular neuronal degenerative diseases such as Alzheimer'"'"'s disease.

9. The use as claimed in one of claims 4 to 8, characterized in that

neuregulin-β

is used as an indicator and/or target for exerting an influence on changes in calcium concentration which are mediated by glutamate receptors.

10. The use of neuregulin-β

as claimed in claim 1, 2 or 3 for testing biomaterials in cell contact, in particular implantation materials as inactive medicinal products.

11. The use of neuregulin-β

as claimed in claim 1, 2 or 3 for screening active compounds and/or for determining indicators and/or targets.

12. The use as claimed in one of claims 4 to 11 for determining provisional results for diagnostic methods.

13. The use of neuregulin-β

as claimed in claim 1, 2 or 3 as an indicator in a method for detecting neuronal processes.

14. The use of neuregulin-β

as claimed in claim 1, 2 or 3 as a target in a method for exerting an influence on neuronal processes.

15. The use as claimed in claim 13 or 14 for detecting, or exerting an influence on, neuronal diseases, in particular neuronal degenerative diseases such as Alzheimer'"'"'s disease.

16. The use as claimed in claim 13 or 14 in controlling the course of neuronal degenerative diseases.