Method of treating Parkinson's disease in humans by convection-enhanced infusion of glial cell-line derived neurotrophic factor to the putamen

• US 20050137134A1
• Filed: 10/13/2004
• Published: 06/23/2005
• Est. Priority Date: 02/24/2003
• Status: Active Grant

• Current Assignee: Amgen Inc., Northern Bristol N.H.S. Trust, Northern Bristol N.H.S. Trust Frenchay Hospital, University Of Kentucky Research Foundation (University of Kentucky)
• Original Assignee: Amgen Inc., North Bristol NHS Trust, University of Kentucky
• Inventors: Gash, Don M., Gill, Steven S., Gerhardt, Greg A.
• Granted Patent: US 8,946,151 B2
• Time in Patent Office: Days
• US Class Current: 514/8.400
• CPC Class Codes: A61K 38/185 Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs

Abstract

A method of treating Parkinson'"'"'s disease in humans is disclosed, wherein glial cell-line derive neurotrophic factor (GDNF) is chronically administered directly to one or both putamen of a human in need of treatment thereof via convection-enhanced infusion using at least one implantable pump and at least one catheter. In one aspect of the present invention the GDNF is infused directly into one or both putamen through one or more indwelling intraparenchymal mutltiport brain catheters connected to one or moreimplantable pumps wherein the flow rate is pulsed.

Claims

1. A method of treating Parkinson'"'"'s disease in a human that comprises administering a pharmaceutical composition comprising a pharmaceutically effective amount of a GDNF protein product and at least one pharmaceutically acceptable vehicle, excipient, or diluent to one or both putamen of a human in need thereof via convection-enhanced infusion using at least one implantable pump and at least one catheter.

2. The method of claim 1 wherein said GDNF protein product is r-metHuGDNF.

3. The method of claim 2 wherein said vehicle, excipient, or diluent comprises sodium chloride and sodium citrate.

4. A method of treating Parkinson'"'"'s disease in a human that comprises:

assessing dopaminergic function in one or both putamen of said human, pre-operatively;

identifying at least one site of dopaminergic dysfunction within one or both putamen;

administering a pharmaceutical composition comprising a pharmaceutically effective amount of a GDNF protein product and at least one pharmaceutically acceptable vehicle, excipient, or diluent to one or more of said sites via convection-enhanced infusion using at least one implantable pump and at least one catheter; and

,

optionally, assessing dopaminergic function at one or more of said sites post-operatively, at least once.

5. The method of claim 4 wherein said GDNF protein product is r-metHuGDNF.

6. The method of claim 5 wherein said vehicle, excipient;

or diluent comprises sodium chloride and sodium citrate.

7. The method any one of claims 4 through 6, wherein assessing dopaminergic function comprises assessing dopamine uptake or dopamine storage.

8. The method of claim 7, wherein said site of dopaminergic dysfunction is the postero-dorsal region of one or both putamen.

9. The method of claim 7 wherein said site of dopaminergic dysfunction is the central region of one or both putamen.

10. A method of increasing the function of dopaminergic neurons in a human that comprises administering a pharmaceutical composition comprising a pharmaceutically effective amount of a GDNF protein product and at least one pharmaceutically acceptable vehicle, excipient, or diluent to one or both putamen of a human in need thereof via convection-enhanced infusion using at least one implantable pump and at least one catheter.

11. The method of claim 10 wherein said GDNF protein product is r-metHuGDNF.

12. The method of claim 11 wherein said vehicle, excipient, or diluent comprises sodium chloride and sodium citrate.

13. The method of claim 12, wherein said pharmaceutical composition is administered to the postero-dorsal region of one or both putamen.

14. The method of claim 12, wherein said pharmaceutical composition is administered to the postero-dorsal region of one or both putamen.

15. A method of increasing the uptake of dopamine by dopaminergic neurons in a human that comprises administering a pharmaceutical composition comprising a pharmaceutically effective amount of a GDNF protein product and at least one pharmaceutically acceptable vehicle, excipient, or diluent to one or both putamen of a human in need thereof via convection-enhanced infusion using at least one implantable pump and at least one catheter.

16. The method of claim 15 wherein said GDNF protein product is r-metHuGDNF.

17. The method of claim 16 wherein said vehicle, excipient, or diluent comprises sodium chloride and sodium citrate.

18. The method of claim 17, wherein said pharmaceutical composition is administered to the postero-dorsal region of one or both putamen.

19. The method of claim 17, wherein said pharmaceutical composition is administered to the postero-dorsal region of one or both putamen.

20. A method of regenerating dopaminergic neurons in a human that comprises administering a pharmaceutical composition comprising a pharmaceutically effective amount of a GDNF protein product and at least one pharmaceutically acceptable vehicle, excipient, or diluent to one or both putamen of a human in need thereof via convection-enhanced infusion using at least one implantable pump and at least one catheter.

21. The method of claim 20 wherein said GDNF protein product is r-metHuGDNF.

22. The method of claim 21 wherein said vehicle, excipient, or diluent comprises sodium chloride and sodium citrate.

23. The method of claim 22, wherein said pharmaceutical composition is administered to the postero-dorsal region of one or both putamen.

24. The method of claim 22, wherein said pharmaceutical composition is administered to the postero-dorsal region of one or both putamen.

25. A method of protecting dopaminergic neurons susceptible to degeneration in a human that comprises administering a pharmaceutical composition comprising a pharmaceutically effective amount of a GDNF protein product and at least one pharmaceutically acceptable vehicle, excipient, or diluent to one or both putamen of a human in need thereof via convection-enhanced infusion using at least one implantable pump and at least one catheter.

26. The method of claim 25 wherein said GDNF protein product is r-metHuGDNF.

27. The method of claim 26 wherein said vehicle, excipient, or diluent comprises sodium chloride and sodium citrate.

28. The method of claim 27, wherein said pharmaceutical composition is administered to the postero-dorsal region of one or both putamen.

29. The method of claim 27, wherein said pharmaceutical composition is administered to the postero-dorsal region of one or both putamen.

30. A method of treating Parkinson'"'"'s disease in a human that comprises administering a pharmaceutical composition comprising a pharmaceutically effective amount of a GDNF protein product and at least one pharmaceutically acceptable vehicle, excipient, or diluent to the central region of at least one putamen of a human in need thereof via convection-enhanced infusion using at least one implantable pump and at least one catheter.

31. The method of claim 30 wherein said GDNF protein product is r-metHuGDNF.

32. The method of claim 31 wherein said vehicle, excipient, or diluent comprises sodium chloride and sodium citrate.

33. The method of claim 32, wherein said pharmaceutical composition is administered to the postero-dorsal region of one or both putamen.

34. The method of claim 32, wherein said pharmaceutical composition is administered to the postero-dorsal region of one or both putamen.

35. A method of treating Parkinson'"'"'s disease in a human that comprises administering a pharmaceutical composition comprising a pharmaceutically effective amount of a GDNF protein product and at least one pharmaceutically acceptable vehicle, excipient, or diluent to the postero-dorsal region of at least one putamen of a human in need thereof via convection-enhanced infusion using at least one implantable pump and at least one catheter.

36. The method of claim 35 wherein said GDNF protein product is r-metHuGDNF.

37. The method of claim 36 wherein said vehicle, excipient, or diluent comprises sodium chloride and sodium citrate.

38. The method of claim 37, wherein said pharmaceutical composition is administered to the postero-dorsal region of one or both putamen.

39. The method of claim 37, wherein said pharmaceutical composition is administered to the postero-dorsal region of one or both putamen.

40. The use of a pharmaceutically effective amount of a GDNF protein product and at least one pharmaceutically acceptable vehicle, excipient, or diluent in the preparation of a pharmaceutical composition for treating Parkinson'"'"'s disease, wherein the composition is for administration to one or both putamen of a human in need thereof via convection-enhanced infusion using at least one implantable pump and at least one catheter.

47. The use of any of claims 40 through 46, wherein the pharmaceutical composition is for administration to one or more sites of dopaminergic dysfunction within one or both putamen, wherein the sites of dopaminergic dysfunction within one or both putamen had been pre-operatively identified by assessing dopamine uptake or dopamine storage at said sites.

48. The use of claim 47 wherein said site of dopaminergic dysfunction is the postero-dorsal region of one or both putamen.

49. The use of claim 47 wherein said site of dopaminergic dysfunction is the central region of one or both putamen.

50. The use of any of claims 40 through 49, wherein said GDNF protein product is r-metHuGDNF.

51. The use of claim 50, wherein said vehicle, excipient, or diluent comprises sodium chloride and sodium citrate.

41. The use of a pharmaceutically effective amount of a GDNF protein product and at least one pharmaceutically acceptable vehicle, excipient, or diluent in the preparation of a pharmaceutical composition for increasing the function of dopaminergic neurons, wherein the composition is for administration to one or both putamen of a human in need thereof via convection-enhanced infusion using at least one implantable pump and at least one catheter.

42. The use of a pharmaceutically effective amount of a GDNF protein product and at least one pharmaceutically acceptable vehicle, excipient, or diluent in the preparation of a pharmaceutical composition for increasing the uptake of dopamine by dopaminergic neurons, wherein the composition is for administration to one or both putamen of a human in need thereof via convection-enhanced infusion using at least one implantable pump and at least one catheter.

43. The use of a pharmaceutically effective amount of a GDNF protein product and at least one pharmaceutically acceptable vehicle, excipient, or diluent in the preparation of a pharmaceutical composition for regenerating dopaminergic neurons, wherein the composition is for administration to one or both putamen of a human in need thereof via convection-enhanced infusion using at least one implantable pump and at least one catheter.

44. The use of a pharmaceutically effective amount of a GDNF protein product and at least one pharmaceutically acceptable vehicle, excipient, or diluent in the preparation of a pharmaceutical composition for protecting dopaminergic neurons susceptible to degeneration, wherein the composition is for administration to one or both putamen of a human in need thereof via convection-enhanced infusion using at least one implantable pump and at least one catheter.

45. The use of a pharmaceutically effective amount of a GDNF protein product and at least one pharmaceutically acceptable vehicle, excipient, or diluent in the preparation of a pharmaceutical composition for treating Parkinson'"'"'s disease, wherein the composition is for administration to the central region of at least one putamen of a human in need thereof via convection-enhanced infusion using at least one implantable pump and at least one catheter.

46. The use of a pharmaceutically effective amount of a GDNF protein product and at least one pharmaceutically acceptable vehicle, excipient, or diluent in the preparation of a pharmaceutical composition for treating Parkinson'"'"'s disease, wherein the composition is for administration to the postero-dorsal region of at least one putamen of a human in need thereof via convection-enhanced infusion using at least one implantable pump and at least one catheter.