Inner Ear Hair Cell Regeneration — Maybe We Can Know More

[Nick47]

What other types of hearing loss or deafness exist besides the loss or death of inner ear hair cells and auditory nerve cells?

Acquired, however so.

 

[Gorbeh3]

Acquired, however so.

I'm not sure what you mean by this. Do you mean acquired hearing loss? Doesn't this simply mean that the individual lost their hearing after birth?

 

[Nick47]

I'm not sure what you mean by this. Do you mean acquired hearing loss? Doesn't this simply mean that the individual lost their hearing after birth?

Spot on.

 

[pants]

I just found this article. I'm not sure if there's anything new in it:

Genetic Reprogramming Regenerates Lost Hair Cells in the Mature Mouse Inner Ear

 

[Auricle]

Thanks for the link.

Stem Cell-Based Hair Cell Regeneration and Therapy in the Inner Ear mentions the same 3 transcription factors, Atoh1, Gfi1, and Pou4f3, but goes into more detail than the study pointed to by @pants. That study mentions regeneration but most likely means supporting cells transdifferentiating into hair-like cells instead of through a combination of cell cycle re-entry / mitosis followed by partial transdifferentiation. The reason this matters is that without mitotic activity, the number of SCs will eventually be depleted, and they are necessary to maintain the structural integrity, endolymphatic potential and cellular HC/SC patterning needed for proper functioning of the organ of Corti.

Another issue I've seen mentioned frequently in recent papers is that these hair-like cells, while in some cases exhibiting similar transcriptomes and mechanotransduction characteristics, are not sufficiently mature to function as proper hair cells. It is suggested that further interventions using additional TFs and epigenetic modifications will be necessary to eventually make restoration of hearing in humans a reality. My take of the literature is that while much progress regarding our understanding in this area is being made, curing hearing loss in humans, if it is at all possible (which isn't at all clear to me), is at least 10 years off.

 

[delta784]

Thanks for the link.

Stem Cell-Based Hair Cell Regeneration and Therapy in the Inner Ear mentions the same 3 transcription factors, Atoh1, Gfi1, and Pou4f3, but goes into more detail than the study pointed to by @pants. That study mentions regeneration but most likely means supporting cells transdifferentiating into hair-like cells instead of through a combination of cell cycle re-entry / mitosis followed by partial transdifferentiation. The reason this matters is that without mitotic activity, the number of SCs will eventually be depleted, and they are necessary to maintain the structural integrity, endolymphatic potential and cellular HC/SC patterning needed for proper functioning of the organ of Corti.

Another issue I've seen mentioned frequently in recent papers is that these hair-like cells, while in some cases exhibiting similar transcriptomes and mechanotransduction characteristics, are not sufficiently mature to function as proper hair cells. It is suggested that further interventions using additional TFs and epigenetic modifications will be necessary to eventually make restoration of hearing in humans a reality. My take of the literature is that while much progress regarding our understanding in this area is being made, curing hearing loss in humans, if it is at all possible (which isn't at all clear to me), is at least 10 years off.

May I ask if you think dysacusis is related to any of those?

 

[Auricle]

As I understand it, dysacusis (which, in my case, presents as saturation and distortion of high frequencies in the left ear) is a neurological symptom. It may result from damage to the spiral ganglion neurons, specifically the dendrites that connect to the inner hair cells (IHCs), which are responsible for sending auditory signals to the brain.

This article has a bunch of details you may find interesting.

 

[Nick47]

"Once you've identified the cell type that can be the basis of your GMP manufacturable process, and then you can tweak that to take it to the therapeutic indication, you can develop a cell therapy and bring that to market in five years," he says. "It's not like the old days with small molecules where it can take ten, 15, 20 years to get a serious therapy on the market.

"When you're treating patients… is because there are no other treatments for them, when you go into phase two and do your safety study [and] efficacy study you're actually treating patients already in terms of their disease. And if you get it right, you can get a fast-track approval. Or a conditional approval… so that you may not even have to do a phase 3 [testing]."

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