Methods of treating cochlear synaptopathy

Abstract

The present application describes the use of gamma secretase inhibitors and gamma secretase modulators for the treatment of cochlear synaptopathy.

1 . A method for treating cochlear synaptopathy in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a gamma secretase inhibitor, a gamma secretase modulator, or a pharmaceutically acceptable salt of any of the foregoing. 
     
     
         2 . The method of  claim 1 , wherein said cochlear synaptopathy is hidden hearing loss. 
     
     
         3 . The method of  claim 1 , wherein said cochlear synaptopathy is tinnitus. 
     
     
         4 .- 7 . (canceled) 
     
     
         8 . The method of  claim 1 , comprising administering a gamma secretase inhibitor or a pharmaceutically acceptable salt thereof. 
     
     
         9 . The method of  claim 1 , comprising administering a gamma secretase modulator or a pharmaceutically acceptable salt thereof. 
     
     
         10 . (canceled) 
     
     
         11 . The method of  claim 1 , comprising administering a gamma secretase inhibitor or a pharmaceutically acceptable salt thereof. 
     
     
         12 . (canceled) 
     
     
         13 . The method of  claim 1 , wherein said gamma secretase inhibitor, gamma secretase modulator, or a pharmaceutically acceptable salt of any of the foregoing, is administered to or near the round window of the cochlea. 
     
     
         14 . The method of  claim 1 , wherein said gamma secretase inhibitor, gamma secretase modulator, or a pharmaceutically acceptable salt of any of the foregoing, is administered via the oral route. 
     
     
         15 . The method of  claim 1 , wherein said gamma secretase inhibitor, gamma secretase modulator, or a pharmaceutically acceptable salt of any of the foregoing, is administered intratympanically. 
     
     
         16 . The method of  claim 13 , comprising administering a gamma secretase modulator. 
     
     
         17 . (canceled) 
     
     
         18 . The method of  claim 13 , comprising administering a gamma secretase inhibitor. 
     
     
         19 . (canceled) 
     
     
         20 . The method of  claim 14 , comprising administering a gamma secretase modulator. 
     
     
         21 . (canceled) 
     
     
         22 . The method of  claim 14 , comprising administering a gamma secretase inhibitor, or a pharmaceutically acceptable salt thereof. 
     
     
         23 . (canceled) 
     
     
         24 . The method of  claim 15 , comprising administering a gamma secretase modulator. 
     
     
         25 . (canceled) 
     
     
         26 . The method of  claim 15 , comprising administering a gamma secretase inhibitor, or a pharmaceutically acceptable salt thereof. 
     
     
         27 . (canceled) 
     
     
         28 . The method of  claim 1 , wherein said gamma secretase inhibitor, or a pharmaceutically acceptable salt thereof, is administered in a pharmaceutical composition comprising a pharmaceutically acceptable aqueous solution comprising:
 (A) approximately 15% to 25% by weight (w/w) of poloxamer 407; or   (B) (i) approximately 15% to 25% by weight (w/w) of poloxamer 407 and
 (ii) approximately 0.5% to 4% by weight (w/w) of hydroxypropyl methylcellulose having a nominal viscosity of 40-60 cP or grade 80-120 cP; or 
   (C) (i) approximately 10%-20% by weight (w/w) of poloxamer 407, and
 (ii) approximately 0.1%-0.3% by weight (w/w) of Carbopol© 974P; or 
   (D) (i) approximately 0.5% to 8% by weight (w/w) of a hyaluronic acid; or   (E) (i) approximately 0.5% to 4% by weight (w/w) of a hyaluronic acid, and
 (ii) approximately 5% to 20% by volume of polyethylene glycol 400; 
   wherein said gamma secretase inhibitor is present in approximately 0.01% to about 20% w/v of said aqueous solution.   
     
     
         29 . (canceled) 
     
     
         30 . The method of  claim 28 , wherein said pharmaceutically acceptable aqueous solution comprises approximately 15% to 25% by weight (w/w) of poloxamer 407. 
     
     
         31 . (canceled) 
     
     
         32 . The method of  claim 1 , comprising treating hyperacusis resulting from loss of inner hair cell afferent synapses in a patient in need thereof. 
     
     
         33 . The method of  claim 1 , wherein said cochlear synaptopathy is sensorineural hearing loss. 
     
     
         34 . The method of  claim 1 , comprising treating sensorineural hearing loss resulting from loss of inner hair cell afferent synapses in a patient in need thereof.