Treatment of neurological deficits in the striatum or substanta nigra pars compacta

• US 20060069008A1
• Filed: 09/28/2004
• Published: 03/30/2006
• Est. Priority Date: 09/28/2004
• Status: Abandoned Application

• Current Assignee: Ethicon Incorporated (Johnson & Johnson)
• Original Assignee: Ethicon Incorporated (Johnson & Johnson)
• Inventors: Messina, Darin J., Mistry, Sanjay
• Application Number:
  US10/952,064
• Publication Number:
  US 20060069008A1
• Time in Patent Office: Days
• US Class Current: 514/9.100
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 38/1825 Fibroblast growth factor [FGF]
• CPC Class Codes: A61K 38/1875 Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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

Abstract

The present invention is directed to methods of treating neurological deficits resulting from injury or disease to the striatum or substanta nigra pars compacta of a human by administering human recombinant GDF5 to the striatum or substanta nigra pars compacta of a human in amounts effective to induce cell populations having the capacity to differentiate towards a dopaminergic phenotype to in fact differentiate towards a dopaminergic phenotype, and to neurotrophic compositions and matrices suitable for use in such treatments.

Claims

1. A method of treating neurological deficits resulting from injury or disease to the striatum or substanta nigra pars compacta of a human comprising administering GDF5-HR to said striatum or said substanta nigra pars compacta of said human in amounts effective to induce cell populations comprising the capacity to differentiate towards a dopaminergic phenotype to in fact differentiate towards said dopaminergic phenotype.

2. The method of claim 1 wherein said GDF5-HR is administered in a single dose.

3. The method of claim 1 wherein the GDF5-HR is administered in a sustained release dosage.

4. The method of claim 1 wherein the GDF5-HR is administered as a neurotrophic composition comprising a physiologically acceptable carrier.

5. The method of claim 4 wherein the carrier is selected from the group consisting of clinical grade sterile water, sterile saline, sterile phosphate buffered saline, dextrose in sterile water, sterile liquid media and physiologically acceptable isotonic liquids.

6. The method of claim 1 wherein the GDF5-HR is administered in a matrix.

7. The method of claim 6 wherein said matrix is in the form selected from the group consisting of a particle, scaffold, cube, cylinder, tube, block, film, hydrogel or sheet.

8. The method of claim 1 wherein said GDF5-HR is administered intracranial by injection via a micro catheter, intracatheterization, intrathecal delivery, or intracerebroventricularly via a mini-pump, or intrathecally, or by intranasal.

9. The method of claim 1 wherein said cell population comprises cells selected from the group consisting of stem or progenitor cell is adult neural progenitors, hippocampal progenitor cells, hippocampel stem cells, mesenchymal stem cells, hematopoietic stem cells, embryonic stem cells, progenitors cells derived from embryonic stem cells, postpartum-derived cells, umbilical cord stem cells, umbilical cord progenitor cells, placenta stem cells, placenta progenitor cells, muscle stem cells, liver stem cells, pancreatic stem cells, limbal stem cells, retinal stem cells, muscle progenitor cells, pancreatic progenitor cells, limbal progenitor cells, retinal progenitor cells, and liver progenitor cells.

10. The method of claim 1 wherein said GDF5-HR is selected from the group consisting of MP52, BMP-14 and CDMP-1.

11. The method of claim 1 wherein said GDF5-HR comprises MP52.

12. The method of claim 4 wherein said GDF5-HR comprises MP52.

13. The method of claim 12 wherein said neurotrophic composition comprises from about 0.5 to about 1,000 nanograms of said MP52.

14. The method of claim 12 wherein said neurotrophic composition further comprises Sonic Hedgehog and FGF8.

15. A neutrophic composition suitable for treating neurological deficits resulting from injury or disease to the striatum or substanta nigra pars compacta of a human, comprising:

GDF5-HR in amounts effective to induce cell populations comprising the capacity to differentiate towards a dopaminergic phenotype to in fact differentiate towards said dopaminergic phenotype,

Sonic Hedgehog;

FGF8; and

a physiologically acceptable carrier.

16. The neurotrophic composition of claim 15 wherein said GDF5-HR is selected from the group consisting of MP52, BMP-14 and CDMP-1.

17. The method of claim 15 wherein said GDF5-HR comprises MP52.

18. The method of claim 17 wherein said neurotrophic composition comprises from about 0.5 to about 1,000 nanograms of said MP52.

19. The composition of claim 17 further comprising Sonic Hedge Hog and FGF8.

20. The composition of claim 15 further comprising Sonic Hedge Hog and FGF8.