Assay for compounds that protect against sensory hair cell death and compounds identified by same
AssigneeFred Hutchinson Cancer Research Center
InventorsHenry Ou, Felipe Santos, Edwin Rubel, David Raible, Julian Simon
Life of this patent
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Abstract
The present invention provides methods of identifying compounds that protect against ototoxicity induced by one or more noxious stimuli, and methods of treating an individual with compounds identified using the present screening methods. Also provided are compounds demonstrated to have otoprotective effects.
Claims27
A method of identifying a compound that inhibits sensory hair cell death, the method comprising:
- a) preferentially labeling the lateral line sensory hair cells of a zebrafish in comparison to other cells, wherein said labeling is substantially non-toxic to the zebrafish hair cells, wherein said label is detectably distinct in a live cell in comparison to a dying cell or a dead cell;
- b) contacting the zebrafish with a test compound suspected of inhibiting sensory hair cell death;
- c) contacting the zebrafish with a noxious stimulus known to cause sensory hair cell death;
- and
- d) detecting the label, wherein a compound that inhibits sensory hair cell death is identified when the number of live lateral line hair cells is greater in zebrafish contacted with the test compound in comparison to a control zebrafish not contacted by the test compound.
A method of simultaneously screening a plurality of compounds that potentially inhibit sensory hair cell death, the method comprising:
- a) preferentially labeling the lateral line hair cells of a plurality of zebrafish in comparison to other cells of the zebrafish, wherein said labeling is substantially non-toxic to the zebrafish hair cells, wherein said label is detectably distinct in a live cell in comparison to a dying cell or a dead cell;
- b) contacting each member of the plurality of zebrafish with one member of a plurality of test compounds suspected of inhibiting sensory hair cell death;
- c) contacting each member of the plurality of zebrafish with one or more noxious stimuli known to cause sensory hair cell death;
- and
- d) detecting the label in each member of the plurality of zebrafish, wherein a compound that inhibits sensory hair cell death is identified when the number of live lateral line hair cells is greater in zebrafish contacted with the test compound in comparison to a control zebrafish not contacted by the test compound.
A method of preventing a condition associated with sensory hair cell death, the method comprising administering a sufficient amount of a compound selected from the group consisting of:
- cepharanthine, amsacrine, drofenine, phenoxybenzamine, N,N-hexamethyleneamiloride, carvedilol and 9-amino-1,2,3,4-tetrahydroacridine.
A method of preventing a condition associated with sensory hair cell death, the method comprising administering a sufficient amount of a compound comprising a thiophene-carboxamide moiety of Formula I or Formula II, wherein said compound inhibits lateral line hair cell death in a zebrafish.
Dependencies are inferred from the claim text.