METHODS OF TREATING COCHLEAR SYNAPTOPATHY
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.