Treatment of hearing loss
Compositions for regeneration of inner cells and for treating hearing loss comprise at least one modulator of mechanistic target of rapamycin (mTOR) sufficient to induce reprogramming proliferation and regeneration of inner ear cells. The composition include, in some instances, an effective amount of one or more phosphatase and tensin homolog (PTEN) inhibitors, MYC/NOTCH modulators, Atonal Homolog 1 (Atoh1) modulators or combinations thereof.
1. A method of regenerating inner ear cells in a mature mammalian cochlea in a subject in need thereof, comprising contacting the cochlea with an effective amount of at least one activator of mechanistic target of rapamycin (mTOR) sufficient to induce reprogramming proliferation and regeneration of inner ear cells; thereby regenerating the inner ear cells in mature mammalian cochlea; wherein the mTOR activator comprises mhy1485, 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one (3BDO), salidroside, or polynucleotides encoding mTOR.
2. The method of claim 1 , wherein the inner ear cells comprise: stria vascularis, hair cells, supporting cells or ganglion neurons.
3. The method of claim 1 , further comprising administering one or more phosphatase and tensin homolog (PTEN) inhibitors and/or Atonal Homolog 1 (Atoh1) activators, wherein the Atoh1 activators comprise β-catenin or Atoh1 polynucleotides.
4. The method of claim 3 , wherein the one or more PTEN inhibitors comprise: bpV(phen), bpV(pic), VO-OHpic, SF1670, antibodies, antibody fragments, antisense oligonucleotides, or siRNAs.
5. A composition comprising an effective amount of least one mechanistic target of rapamycin (mTOR) activator, wherein the mTOR activator comprises mhy1485, 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one (3BDO), salidroside, or polynucleotides encoding mTOR; and one or more phosphatase and tensin homolog (PTEN) inhibitors or one or more Atonal Homolog 1 (Atoh1) activators, wherein the Atoh1 activators comprise β-catenin or Atoh1 polynucleotides.
6. The composition of claim 5 , wherein the one or more PTEN inhibitors comprise: bpV(phen), bpV(pic), VO-OHpic, SF1670, antibodies, antibody fragments, antisense oligonucleotides, or siRNAs.