Treatment of hearing impairments

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.

What is claimed is:  
     
         1 . A method for treating damage to spiral ganglion neurons, comprising exposing the neurons to a therapeutically effective amount of a trkB or trkC agonist.  
     
     
         2 . The method of  claim 1 , wherein treating damage to spiral ganglion neurons reduces hearing loss.  
     
     
         3 . The method of  claim 1  further comprising administering a therapeutically effective amount of a further trkB or trkC agonist.  
     
     
         4 . The method of  claim 3 , wherein the further trkB or trkC agonist is identical to the trkB or trkC agonist of  claim 1 .  
     
     
         5 . 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.  
     
     
         6 . The method of  claim 5 , wherein the neurotrophin is selected from the group consisting of NT-4/5, BDNF and NT-3.  
     
     
         7 . The method of  claim 6 , wherein the neurotrophin is NT-4/5.  
     
     
         8 . The method of  claim 5 , wherein the pantrophic neurotrophin is MNTS-1.  
     
     
         9 . The method of  claim 1 , wherein the damage is caused by an ototoxic agent.  
     
     
         10 . The method of  claim 9 , wherein the ototoxic agent is a pharmaceutical drug.  
     
     
         11 . The method of  claim 10 , wherein the 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.  
     
     
         12 . The method of  claim 11 , wherein the 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.  
     
     
         13 . The method of  claim 10 , wherein the ototoxic agent is an anti-neoplastic drug.  
     
     
         14 . The method of  claim 13 , wherein the ototoxic agent is cisplatin or a cisplatin-like compound.  
     
     
         15 . 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.  
     
     
         16 . The method of  claim 15 , wherein the agent is retinoic acid or retinoic acid in combination with TGF-α.  
     
     
         17 . A method for preventing damage to spiral ganglion neurons, comprising exposing the neurons to a therapeutically effective amount of a trkB or trkC agonist before exposing the spiral ganglion neurons to a factor capable of damaging the neurons.  
     
     
         18 . A method of treatment, comprising: 
 administering a chemotherapeutic drug; and    admininistering a therapeutically effective amount of a trkB or trkC agonist so that hearing impairment induced by the chemotherapeutic agent is reduced, wherein the chemotherapeutic drug is known to cause hearing impairment.    
     
     
         19 . The method of  claim 18 , wherein the chemotherapeutic agent is cisplatin or a cisplatin analog.  
     
     
         20 . The method of  claim 19  comprising further administering a therapeutically effective amount of a further trkB or trkC agonist.  
     
     
         21 . The method of  claim 20 , wherein the further trkB or trkC agonist is identical to the trkB or trkC agonist of  claim 18 .  
     
     
         22 . A method of treatment, comprising: 
 administering an aminoglycoside; and    admininistering a therapeutically effective amount of a trkB or trkC agonist so that hearing impairment induced by the aminoglycoside is reduced, wherein the aminoglycoside is known to cause hearing impairment.    
     
     
         23 . The method of  claim 22 , wherein the 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 23 , further comprising administering a therapeutically effective amount of a further trkB or trkC agonist.  
     
     
         25 . The method of  claim 24 , wherein the further trkB or trkC agonist is identical to the trkB or trkC agonist of  claim 22 .  
     
     
         26 . A method for reducing the ototoxic effect of an ototoxic agent in a mammal, comprising exposing neurons in the mammal to a thereupeutically effective amount of a trkB or trkC agonist, wherein the ototoxic effect results from neuronal damage in the mammal.  
     
     
         27 . The method of  claim 26 , wherein the neuronal damage comprises damage to spiral ganglion neurons.  
     
     
         28 . The method of  claim 26 , wherein the neuronal damage further comprises damage to vestibular ganglion neurons.  
     
     
         29 . The method of  claim 26 , wherein the mammal is exposed to the ototoxic agent before exposure to the trkB or trkC agonist.  
     
     
         30 . The method of  claim 29 , wherein the mammal is exposed to the ototoxic agent after exposure to the trkB or trkC agonist.  
     
     
         31 . The method of  claim 30 , wherein the mammal is exposed to the ototoxic agent and the trkB or trkC agonist at the same time.  
     
     
         32 . The method of  claim 26 , further comprising administering a therapeutically effective amount of a further trkB or trkC agonist.  
     
     
         33 . The method of  claim 32 , wherein the further trkB or trkC agonist is identical to the trkB or trkC agonist of  claim 26 .  
     
     
         34 . A kit for the treatment of hearing impairment in a mammal comprising: 
 a trkB or trkC agonist; and    instructions for administering to the mammal a therapeutically effective dose of the trkB or trkC agonist if the mammal suffers from hearing impairment caused by an ototoxic agent.