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

• US 8,946,151 B2
• Filed: 10/13/2004
• Issued: 02/03/2015
• 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., Northern Bristol N.H.S. Trust Frenchay Hospital, University Of Kentucky Research Foundation (University of Kentucky)
• Inventors: Gill, Steven S., Gash, Don M., Gerhardt, Greg A.
• Primary Examiner(s): Emch, Gregory S
• Application Number:
  US10/963,986
• Publication Number:
  US 20050137134A1
• Time in Patent Office: 3,765 Days
• Field of Search: None
• US Class Current: 514/8.3
• 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 multiport brain catheters connected to one or more implantable pumps wherein the flow rate is pulsed.

Claims

1. A method of producing a sustained increase in dopamine uptake within one or both putamen in a human suffering from Parkinson'"'"'s disease that comprises locally administering to one or both putamen of a human in need thereof via convection-enhanced infusion using at least one catheter implanted for localized and targeted delivery into the putamen a pharmaceutical composition comprising a pharmaceutically effective amount of a glial cell-line derived neurotrophic factor (GDNF) protein product and at least one pharmaceutically acceptable vehicle, excipient, or diluent, wherein said GDNF protein product is administered in an amount and over a time effective to produce a sustained increase in dopamine uptake in the one or both putamen, and wherein the diffusion of said GDNF protein product resulting from such administration is limited to the putamen.

2. The method of claim 1 wherein said GDNF protein product is recombinant-methionyl human glial cell line-derived neurotrophic factor (r-metHuGDNF).

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

40. The method of claim 1, 4, 10, 15, 20, 25, 30, or 35 wherein the GDNF protein product is administered at a dosage from about 1 μ

g/putamen/day to about 100 μ

g/putamen/day.

43. The method according to any one of claims 1, 4, 10, 15, 20, 25, 30, 35, 41 and 42, wherein the administration of said pharmaceutical composition is pulsed.

4. A method of producing a sustained increase in dopamine uptake within one or both putamen in a human suffering from Parkinson'"'"'s disease 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;

locally administering to one or both putamen of a human in need thereof via convection-enhanced infusion using at least one catheter implanted for localized and targeted delivery into the putamen a pharmaceutical composition comprising a pharmaceutically effective amount of a glial cell-line derived neurotrophic factor (GDNF) protein product and at least one pharmaceutically acceptable vehicle, excipient, or diluent, wherein said GDNF protein product is administered in an amount and over a time effective to produce a sustained increase in dopamine uptake in the one or both putamen, and wherein the diffusion of said GDNF protein product resulting from such administration is limited to the putamen; and

,

optionally, assessing dopaminergic function at one or more 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 of 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 producing a sustained increase in dopamine uptake within one or both putamen, thereby increasing the function of dopaminergic neurons in a human in need thereof that comprises locally administering to one or both putamen of a human in need thereof via convection-enhanced infusion using at least one catheter implanted for localized and targeted delivery into the putamen a pharmaceutical composition comprising a pharmaceutically effective amount of a glial cell-line derived neurotrophic factor (GDNF) protein product and at least one pharmaceutically acceptable vehicle, excipient, or diluent, wherein said GDNF protein product is administered in an amount and over a time effective to produce a sustained increase in dopamine uptake in the one or both putamen, and wherein the diffusion of said GDNF protein product resulting from such administration is limited to the putamen.

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 central region of one or both putamen.

15. A method of increasing the uptake of dopamine by dopaminergic neurons in a human that comprises locally administering to one or both putamen of a human in need thereof via convection-enhanced infusion using at least one catheter implanted for localized and targeted delivery into the putamen a pharmaceutical composition comprising a pharmaceutically effective amount of a glial cell-line derived neurotrophic factor (GDNF) protein product and at least one pharmaceutically acceptable vehicle, excipient, or diluent, wherein diffusion of said GDNF protein product is limited to the putamen of said human.

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 central region of one or both putamen.

20. A method of regenerating dopaminergic neurons in a human that comprises locally administering to one or both putamen of a human in need thereof via convection-enhanced infusion using at least one catheter implanted for localized and targeted delivery into the putamen a pharmaceutical composition comprising a pharmaceutically effective amount of a glial cell-line derived neurotrophic factor (GDNF) protein product and at least one pharmaceutically acceptable vehicle, excipient, or diluent, wherein diffusion of said GDNF protein product is limited to the putamen of said human.

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 central region of one or both putamen.

25. A method of protecting dopaminergic neurons susceptible to degeneration in a human that comprises locally administering to one or both putamen of a human in need thereof via convection-enhanced infusion using at least one catheter implanted for localized and targeted delivery into the putamen a pharmaceutical composition comprising a pharmaceutically effective amount of a glial cell-line derived neurotrophic factor (GDNF) protein product and at least one pharmaceutically acceptable vehicle, excipient, or diluent, wherein diffusion of said GDNF protein product is limited to the putamen of said human.

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 central region of one or both putamen.

30. A method of treating Parkinson'"'"'s disease in a human that comprises locally administering to a region of one or both putamen of a human in need thereof via convection-enhanced infusion using at least one catheter a pharmaceutical composition comprising a pharmaceutically effective amount of a glial cell-line derived neurotrophic factor (GDNF) protein product and at least one pharmaceutically acceptable vehicle, excipient, or diluent, wherein diffusion of said GDNF protein product is limited to the putamen of said human.

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 central region of one or both putamen.

35. A method of treating Parkinson'"'"'s disease in a human that comprises locally administering to one or both putamen of a human in need thereof via convection-enhanced infusion using at least one catheter implanted for localized and targeted delivery into the putamen a pharmaceutical composition comprising a pharmaceutically effective amount of a glial cell-line derived neurotrophic factor (GDNF) protein product and at least one pharmaceutically acceptable vehicle, excipient, or diluent, wherein diffusion of said GDNF protein product is limited to the putamen of said human.

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 central region of one or both putamen.

41. A method of producing a sustained increase in dopamine uptake within one or both putamen in a human suffering from Parkinson'"'"'s disease, said method consisting essentially of the step of locally administering to one or both putamen of a human in need thereof via convection-enhanced infusion using at least one catheter implanted for localized and targeted delivery into the putamen a pharmaceutical composition comprising a pharmaceutically effective amount of a glial cell-line derived neurotrophic factor (GDNF) protein product and at least one pharmaceutically acceptable vehicle, excipient, or diluent, wherein said GDNF protein product is administered in an amount and over a time effective to produce a sustained increase in dopamine uptake in the one or both putamen, and wherein the diffusion of said GDNF protein product resulting from such administration is limited to the putamen of said human.

42. A method of producing a sustained increase in dopamine uptake within one or both putamen in a human suffering from Parkinson'"'"'s disease, said method consisting of the step of locally administering to one or both putamen of a human in need thereof via convection-enhanced infusion using at least one catheter implanted for localized and targeted delivery into the putamen a pharmaceutical composition comprising a pharmaceutically effective amount of a glial cell-line derived neurotrophic factor (GDNF) protein product and at least one pharmaceutically acceptable vehicle, excipient, or diluent, wherein said GDNF protein product is administered in an amount and over a time effective to produce a sustained increase in dopamine uptake in the one or both putamen, and wherein the tissue distribution of said GDNF protein product resulting from such administration is limited to the putamen of said human.