Methods for increasing the survival of neuronal cells

• US 20030008273A1
• Filed: 06/11/2002
• Published: 01/09/2003
• Est. Priority Date: 06/11/2001
• Status: Abandoned Application

• Current Assignee: Ludwig Institute for Cancer Research, Ltd.
• Original Assignee: Ludwig Institute for Cancer Research, Ltd.
• Inventors: Wallen, Asa, Wagner, Joe, Arenas, Ernest, Perlmann, Thomas
• Application Number:
  US10/166,158
• Publication Number:
  US 20030008273A1
• Time in Patent Office: Days
• US Class Current: 435/4
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/203 Retinoic acids ; Salts thereof
• CPC Class Codes: A61K 38/177 Receptors; Cell surface antigens; Cell surface determinants
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: G01N 2333/70567 Nuclear receptors, e.g. retinoic acid receptor [RAR], RXR, nuclear orphan receptors
• CPC Class Codes: G01N 2500/00 Screening for compounds of potential therapeutic value
• CPC Class Codes: G01N 2800/2835 Movement disorders, e.g. Parkinson, Huntington, Tourette
• CPC Class Codes: G01N 33/5041 involving analysis of members of signalling pathways
• CPC Class Codes: G01N 33/5058 Neurological cells
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease

Abstract

The invention relates to methods of increasing the survival of dopamine secreting cells, comprising the steps of administering a retinoid X receptor (RXR) ligand to dopamine secreting cells, wherein the binding of the RXR ligand increases the survival of the dopamine secreting cells. Therapeutic approaches to neurodegenerative diseases are also disclosed.

Claims

1. A method of increasing the survival of dopamine secreting cells, comprising the steps of administering a retinoid X receptor (RXR) ligand to dopamine secreting cells in an amount sufficient for the RXR ligand to bind RXR and increase the survival of the dopamine secreting cells.

2. The method of claim 1, wherein the RXR ligand selectively activates RXR.

3. The method of claim 1, wherein the dopamine secreting cells are cultured in vitro.

4. The method of claim 1, wherein the RXR ligand is a naturally-occurring ligand.

5. The method of claim 4, wherein the naturally-occurring ligand is isolated from ventral embryonic midbrain cells.

6. The method of claim 4, wherein the naturally-occurring ligand is 9-cis retinoic acid or docosahexaenoic acid.

7. The method of claim 1, wherein the RXR ligand is a non-naturally-occurring-RXR ligand.

8. The method of claim 7, wherein the non-naturally-occurring-RXR ligand is LG1069, LG100268, SR11203, SR11217, SR11234, SR11235, SR11236 or SR11237.

9. The method of claim 1, wherein the dopamine secreting cells are derived from the basal ganglia.

10. The method of claim 9, wherein the cells derived from the basal ganglia are derived from cells selected from the group consisting of:

dopamine secreting cells from the striatum, globus pallidus, substantia innominate, ventral pallidum, nucleus basalis of Meynert, ventral tegmental area, the subthalmic nucleus, and the substantia nigra.

11. The method of claim 1, further comprising administering an RAR antagonist.

13. The method of claim 12, wherein the subject has a neurodegenerative disease.

14. The method of claim 13, wherein the neurodegenerative disease is characterized by loss of dopamine-secreting cells.

15. The method of claim 14, wherein the neurodegenerative disease is Parkinson'"'"'s disease.

16. The method of claim 12, wherein the RXR ligand selectively activates RXR.

17. The method of claim 12, wherein the RXR ligand is a naturally-occurring ligand.

18. The method of claim 17, wherein the naturally-occurring ligand is isolated from ventral embryonic midbrain cells.

19. The method of claim 17, wherein the naturally-occurring ligand is 9-cis retinoic acid or docosahexaenoic acid.

20. The method of claim 12, wherein the RXR ligand is a non-naturally-occurring-RXR ligand.

21. The method of claim 20, wherein the non-naturally-occurring-RXR ligand is LG1069, LG100268, SR11203, SR11217, SR11234, SR11235, SR11236 or SR11237.

22. The method of claim 12, wherein the dopamine-secreting cells are cells in the basal ganglia.

23. The method of claim 22, wherein the basal ganglia cells are located in the striatum, globus pallidus, substantia innominate, ventral pallidum, nucleus basalis of Meynert, ventral tegmental area, the subthalmic nucleus, or the substantia nigra.

24. The method of claim 12, further comprising administering an RAR antagonist.

12. A method of increasing the survival of dopamine-secreting cells in a subject in need thereof, comprising the steps of administering a retinoid X receptor (RXR) ligand to the subject, in an amount sufficient for the RXR ligand to bind RXR and increase the survival of the dopamine-secreting cells.