Treatment of hearing impairments

• US 6,429,191 B1
• Filed: 03/30/2001
• Issued: 08/06/2002
• Est. Priority Date: 01/05/1996
• Status: Expired due to Term

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Gao, Wei-Qiang
• Primary Examiner(s): FAY, ZOHREH A
• Application Number:
  US09/823,717
• Publication Number:
  US 20020039995A1
• Time in Patent Office: 494 Days
• Field of Search: 514/2, 514/12, 514/192, 514/198, 514/199
• US Class Current: 514/2.4
• 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: C12N 2501/13 Nerve growth factor [NGF]; Brain-derived neurotrophic factor [BDNF]; Cilliary neurotrophic factor [CNTF]; Glial-derived neurotrophic factor [GDNF]; Neurotrophins [NT]; Neuregulins
• CPC Class Codes: C12N 2503/02 Drug screening
• CPC Class Codes: C12N 5/062 Sensory transducers, e.g. photoreceptors; Sensory neurons, e.g. for hearing, taste, smell, pH, touch, temperature, pain

Abstract

Compositions and methods are provided for prophylactic or therapeutic treatment of a mammal for hearing impairments involving neuronal damage, loss, or degeneration, preferably of spinal ganglion neurons, by administration of a therapeutically effective amount of a trkB or trkC agonist, particularly a neurotrophin, more preferably NT-4/5. Also provided are improved compositions and methods for treatments requiring administration of a pharmaceutical having an ototoxic side-effect, wherein the improvement includes administering a therapeutically effective amount of a trkB or trkC agonist to treat the ototoxicity.

Claims

1. A method for treating hearing impairment in a post-natal mammal, the method comprising administering to the mammal a therapeutically effective amount of a trkB or trkC agonist, wherein said hearing impairment is the result of neuronal damage.

2. The method of claim 1, wherein the agonist is selected from the group consisting of a neurotrophin, a chimeric neurotrophin, a pantrophic neurotrophin, a small molecule agonist and an antibody agonist or an antigen-binding fragment thereof.

3. The method of claim 2, wherein said neurotrophin is selected from the group consisting of NT-4/5, BDNF or NT-3.

4. The method of claim 3, wherein the neurotrophin is NT-4/5.

5. The method of claim 2, wherein said pantrophic neurotrophin is MNTS-1.

6. The method of claim 1, wherein said neuronal damage is damage to spiral ganglion neurons.

7. The method of claim 6 wherein said damage is caused by an ototoxic agent.

8. The method of claim 7, wherein the ototoxic agent is a pharmaceutical drug.

9. The method of claim 8, wherein said pharmaceutical drug is selected from the group consisting of an aminoglycoside antibiotic, a chemotherapeutic agent, a salicylate or salicylate-like compound, a loop diuretic, and a quinine or quinine-like compound.

10. The method of claim 9, wherein said aminoglycoside antibiotic is selected from the group consisting of neomycin, paromomycin, ribostamycin, lividomycin, kanamycin, amikacin, tobramycin, viomycin, gentamicin, sisomicin, netilmicin, streptomycin, dibekacin, fortimicin, and dihydrostreptomycin.

11. The method of claim 8, wherein the ototoxic agent is an anti-neoplastic drug.

12. The method of claim 11, wherein the ototoxic agent is cisplatin or a cisplatin-like compound.

13. The method of claim 1, wherein the trkB or trkC agonist is administered with an agent that promotes hair cell growth, proliferation, survival, or differentiation.

14. The method of claim 13 wherein said agent is retinoic acid or retinoic acid in combination with TGF-α

.

15. The method of claim 1 further comprising administering a therapeutically effective amount of a further trkB or trkC agonist.

16. A method of treating damage to spiral ganglion neurons in a post-natal mammal, comprising administering to the mammal a therapeutically effective amount of a trkB or trkC agonist.

17. The method of claim 16 wherein the agonist is selected from the group consisting of a neurotrophin, a chimeric neurotrophin, a pantrophic neurotrophin, a small molecule agonist and an antibody agonist or an antigen-binding fragment thereof.

18. The method of claim 17, wherein said neurotrophin is selected from the group consisting of NT-4/5, BDNF and NT-3.

19. The method of claim 18 wherein said neurotrophin is NT-4/5.

20. The method of claim 17 wherein said pantrophic neurotrophin is MNTS-1.

21. The method of claim 16 wherein said damage to spiral ganglion neurons is caused by an ototoxic agent.

22. The method of claim 21, wherein said ototoxic agent is selected from the group consisting of an aminoglycoside antibiotic, a chemotherapeutic agent, a salicylate or salicylate-like compound, a loop diuretic, and a quinine or quinine-like compound.

23. The method of claim 22 wherein said aminoglycoside antibiotic is selected from the group consisting of neomycin, paromomycin, ribostamycin, lividomycin, kanamycin, amikacin, tobramycin, viomycin, gentamicin, sisomicin, netilmicin, streptomycin, dibekacin, fortimicin and dihydrostreptomycin.

24. The method of claim 21 wherein the ototoxic agent is an anti-neoplastic drug.

25. The method of claim 24 wherein the ototoxic agent is cisplatin or a cisplatin-like compound.

26. A method of preventing hearing impairment in a post-natal mammal comprising administering to the mammal a therapeutically effective amount of a trkB or trkC agonist, wherein it is known that said mammal will be exposed to an external factor that can injure spiral ganglion neurons.

27. The method of claim 26 wherein the agonist is selected from the group consisting of a neurotrophin, a chimeric neurotrophin, a pantrophic neurotrophin, a small molecule agonist and an antibody agonist or an antigen-binding fragment thereof.

28. The method of claim 27 wherein said neurotrophin is selected from the group consisting of NT-4/5, BDNF and NT-3.

29. The method of claim 28 wherein said neurotrophin is NT-4/5.

30. The method of claim 26 wherein said pantrophic neurotrophin is MNTS-1.

31. The method of claim 26 wherein said external factor is an ototoxic agent.

32. The method of claim 31 wherein said ototoxic agent is to be administered therapeutically to said mammal.

33. The method of claim 32 wherein the ototoxic agent is a pharmaceutical drug.

34. The method of claim 33, wherein said pharmaceutical drug is selected from the group consisting of an aminoglycoside antibiotic, a chemotherapeutic agent, a salicylate or salicylate-like compound, a loop diuretic and a quinine or quinine-like compound.

35. The method of claim 34 wherein said aminoglycoside antibiotic is selected from the group consisting of neomycin, paromomycin, ribostamycin, lividomycin, kanamycin, amikacin, tobramycin, viomycin, gentamicin, sisomicin, netilmicin, streptomycin, dibekacin, fortimicin and dihydrostreptomycin.

36. The method of claim 33 wherein the ototoxic agent is an anti-neoplastic drug.

37. The method of claim 36 wherein the ototoxic agent is cisplatin or a cisplatin-like compound.

38. The method of claim 26 wherein said external factor is administered to the mammal in combination with the agonist.