Regrowing Hairs Cells Through DNA Reprogramming

https://www.nature.com/articles/s41467-019-13157-7

A method of hearing restoration through DNA is underway.

This sounds similar to method Frequency Therapeutics is targeting by activating progenitor cells in the cochlea, except this is specifically through DNA.

 

This is Dr. Chen's lab at Harvard. I emailed him and got a great (but necessarily a little vague at this stage) response but the bottom of the email said for private communication only. I asked him if i can post his response and am waiting to hear back.

He is still in pre-clinical atm.

 

I got permission to share his email (cut and paste below):

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Thank you for your interest in our work and for your questions. Here are the general information I can provide which I hope will be some help to you.

Our work is done in animal model, and we want to find drug-like molecules to restore hearing in animals first before we can contemplate to move to human. From current evidence our approach should be able to regenerate both inner and outer hair cells, which is something we are truly excited about. Also regeneration shouldn’t be too dependent on when the damage occurred, suggesting even for people with hearing loss for a long term it could still work to a degree. Further new hair cells can form connections with neurons, which can be used for direct repair and more importantly it may allow to identify important molecules that can help to re-establish neuron-hair cell connections.

When will it happen in humans? We honestly don’t know. If our and other work is any indication, the discovery is accelerating that can only speed up the time to reach clinic. My sincere hope is to have some type of medications within a decade to treat some forms of hearing loss.

We are truly excited about the progress we made and are working very hard to move forward as fast as we can.

With best wishes,
Zheng-Yi

 

That's encouraging. Thanks.

 

Some of the more interesting things about Chen's work:

1) He is testing in vitro using a culture fully encased in bone in the same cochlear shape to give a more accurate model in vitro. This should make it more likely to translate to in vivo testing.

2) His methods could even work for severe loss/cochlear implant candidates:

"Well documented is the presence of undifferentiated flat epithelial cells instead of SCs in the cochlea of patients suffering from severe hearing loss. The flat epithelium loses responsiveness to Atoh1 and does not become HCs. Our study points to the possibility of deeper reprogramming, which could be achieved by activation of the otic genes upstream of Notch during development with Myc in the flat epithelium so these cells can first become SC-like and then transdifferentiate into HCs."

3) in addition to IHC and OHC, this method could regenerate cells of the stria vascularis. This has potentially huge implications for Meneire's, Cisplatin Ototoxicity and Macrolide Ototoxicity.

"Reprogramming and proliferation induced by Myc/NICD co-activation in the adult cochlea is widespread, encompassing SCs, HCs, and fibrocytes in the stria vascularis, providing a useful tool to regenerate diverse inner ear cell types involved in different types of deafness. Given the important roles Myc and Notch play in different tissues, we hope that our study can serve as a model for regeneration of other post-mitotic tissues such as the retina and the central nervous system."

 

Sounds so futuristic. Could them make me reborn? I would like to choose a different university degree, not taking some medications I took and taking care of my ears from noise.

 

What do you mean specifically through DNA?

 

Would this require FDA approval? I'm hoping the answer is no!!!

 

This would, for sure, require FDA approval.

 

"Co-activation of cell cycle activator Myc and inner ear progenitor gene Notch1 induces robust proliferation of diverse adult cochlear sensory epithelial cell types"

 

It probably will. This researcher is working out of Harvard, so a name like that might help.

 

We are talking about making changes to your DNA, it obviously would require FDA approval, assuming this venue is even acceptable for human treatment (in a legal standpoint) in the United States.

 

This doesn't change your genome at all. It just activates dormant genes long enough for them to make structures they did when you were an embryo again. It's not a CRISPR gene editing therapy.

 

https://www.actiononhearingloss.org...earch-breakthrough-in-hair-cell-regeneration/

A well-written little piece on this research - not just a rehash of the original press release.

 

For those who weren’t aware Chen is also on the scientific advisory board for Decibel Therapeutics. It makes me wonder if Decibel’s “novel discovery” for hearing loss might actually be Chen’s DNA reprogramming.

 

They sure do seem like they waste a lot of time. I'd like to know what they do day in and day out.

 

If Decibel could run with this it would be a nice alternative to FX-322. I'm not sure what they have been up to either. It started off as very promising and then........

I wish I had the connections and funding to form my own hearing loss company. That article that
d'Wooluf posted seems very promising. To me it just seems crazy that there are all these breakthroughs but nothing has been developed to help us.

 

Epigenetics.

 

Intersting discovery regarding the JRHNBR signaling pathway.

https://www.latlmes.com/breaking/tinnitus-jrhnbr-pathway-1

 

Cure in 2020 confirmed!

 

Please tell me those pictures are a joke and Decibel Therapeutics is legit.

 

The pictures are legit, but it doesn’t mean they don’t work hard. Work events to relax and blow off steam are common in companies that respect their employees. See it as more of a meme about how slow research moves, strictly for the lolz.

 

True but for this company their priorities are designing an aesthetically pleasing work space and raising money from investors via fanciful sales pitches, said "pretty" workspace, or pedaling some useless oto-protective treatment to grab more investor money. They have not shown any interest in testing out product lines. SHORT THIS COMPANY!!!

 

The beauty of capitalism is that the company that pulls their weight will end up on top, this is not the only hearing regen company out there. Remember that social media is fun PR to raise awareness that the company exists and not to share their scientific progress. Even if they don’t present the big cure, I appreciate the research they have put it. The more coals in the fire the better.

Edit: Also, that otoprotective drug is not useless. People have their lives turned upside down by chemotherapy side effects (eg, going deaf) and this is a huge deal in giving cancer survivors a good life.

 

That's not a given. Have you heard of Enron? Also investor dollars toward this company could be less money going to others in the regenerative hearing loss field. Not great in the short run.

 

I understand your concern, but I disagree. Enron was a massive case of fraud and corruption, not a fair comparison.

Decibel has not stopped frequency, pipeline and otonamy from being funded and going through trials. If they were the only big player I’d be peeved too, but they are not.

 

The otologic side effects of Cisplatin are horrific. Even if it doesn't benefit most of us, many people will have their lives saved by an otoprotective drug for platinum based chemotherapeutics.