Blocking Notch Pathway Leads to New Route to Hair Cell Regeneration to Restore Hearing

An interesting finding:

Blocking Notch Pathway Leads to New Route to Hair Cell Regeneration to Restore Hearing

Sensory hair cell loss is the major cause of hearing loss and balance disorders. The postnatal mammalian inner ear harbors progenitor cells which have the potential for hair cell regeneration and hearing recovery, but the mechanisms that control their proliferation and hair cell regeneration are yet to be determined. Now scientists from the Eaton-Peabody Laboratories at Massachusetts Eye and Ear/Harvard Medical School and Fudan University, Shanghai, China, have shown that blocking the Notch pathway, known to control the elaborate hair cell distribution in the inner ear, plays an essential role that determines cochlear progenitor cell proliferation capacity. Their research was published today in PNAS Early Edition.

"A high level of Notch activity prevents progenitor cell division and hair cell regeneration in the postnatal inner ear," said Zheng-Yi Chen, Ph.D., of the Eaton-Peabody Laboratories at Mass. Eye and Ear and an Associate Professor of Otology and Laryngology at Harvard Medical School. "We learned something new about this mechanism. It is known that inhibition of Notch activity can convert inner ear supporting cells to hair cells. In this paper, we have shown that Notch inhibition also promotes cell division. Under the condition, the inner ear progenitor cells re-enter cell division to regenerate hair cells in postnatal cochlea. This study thus provides a new route to block Notch activity to increase progenitor cell population by cell division, and to regenerate new hair cells. Our work could have potential in leading to developing new strategies to achieve hair cell regeneration for hearing restoration."

The researchers show that Notch inhibition initiates proliferation of supporting cells that give rise to new hair cells in postnatal mouse cochlea in vivo and in vitro. Through lineage tracing, they identified that a majority of the proliferating supporting cells and cell division-generated hair cells induced by Notch inhibition are originated from the Wnt-responsive leucine-rich repeat-containing G protein coupled receptor 5 (Lgr5+) progenitor cells. They demonstrated that Notch inhibition removes the brakes on the canonical Wnt signaling and promotes Lgr5+ progenitor cells to mitotically generate new hair cells.

"Our study reveals a new function of Notch signaling in limiting proliferation and regeneration potential of postnatal cochlear progenitor cells, and provides a new route to regenerate HCs from progenitor cells by interrupting the interaction between the Notch and Wnt pathways," Dr. Chen said.

 

Yes, Dr. Chen is very top notch. He's the one who made some very important discoveries back in 2005 with RB1 gene and hair cell regeneration. He's working close with Dr. Edge, who is connected with Audion Therapeutics. They are very optimistic about their research, so maybe we will see some progress soon.

 

This is real good news. It gives me hope for being able to enjoy silence again in the future, and it's exactly this hope that I need to carry on. Thank God for scientists like Dr. Zheng-Yi Chen.

 

I found this very exciting read from the top notch researcher Zheng-Yi-Chen about his advanced work in the Chen Lab:

Five Questions with Zheng-Yi Chen - Harvard Catalyst

 

This is very interesting.

 

Nice find! This is really exciting because this is a completely new approach. What solves the problem, is that everything has to be regenerated perfectly in the right place and order to regain function. They try to reprogram the inner ear cells to turn their biological clock backwards.

I guess they are talking over results at the "ISIET 2023 symposium, 28-30 APRIL 2023, Marrakech INNER EAR THERAPEUTICS : UPDATES AND CHALLENGES FOR APPLICATIONS".

 

Oh wow, that is also a nice finding. Many of the top researchers in the field will attend.

It would be very amazing if they could turn back the clock in the inner ear, it sounds amazing.

 

A big update about this research:

Scientists Regenerate Hair Cells that Enable Hearing

 

Wow, I feel like this is a really big deal and this guy seems pretty brilliant and determined. Great find.

 

Gene therapy though. Still many decades away. Molecular therapy is closer, just need to find the right molecule for the MYC pathway.

 

You think decades? They already use adenovirus-based gene therapy (what they described in the article) for cancer.

 

I do. Barring a major discovery in molecular therapeutics (which isn’t completely impossible), I think we are at least two decades out from any sort of hearing regeneration therapeutics being available to the general public.

Maybe longer for gene therapy. Gene therapy will probably also be cost prohibitive for most. I know ocular gene therapy can cost millions for a single treatment. Maybe I’m wrong, maybe AI will find something or there will be a major breakthrough... but I am doubtful. Someone prove me wrong.

I am not trying to be negative but I don’t want people to cling to false hope such as what happened with Auris Medical, Frequency Therapeutics, Hough Ear Institute, and Otonomy. I have been around Tinnitus Talk long enough to see many false promises and hype arise, only for people to leave the community disappointed and crushed, time and time again. When I was 22 and got tinnitus, it was always “we’ll have a cure in 10 years”. Well it’s been 15 years with tinnitus and we still have nothing.

I think the bimodal neuromodulation solutions are our best chance at silence in the near future. That paired with sound therapy, CBT, and lifestyle/nutrition changes are going to help more people in the next twenty years.

 

Absolutely not in my opinion. Too much acceleration in AI to compare the next decade of progress to prior decades.

 

Is this the same thing that FX-322 already tried or is there anything different here?

 

The aim is the same, regenerate hair cells responsible for hearing, but a very different approach, I guess more complicated to apply than FX-322.

 

Dr. Zheng-Yi Chen has received a grant by Department of Defense:

Dr. Zheng-Yi Chen Named Principal Investigator of Hearing Restoration Research Program Grant by Department of Defense

 

It says he plans to test two drugs. Does anyone know which drugs those are?

 

AI is not going to help. I don't think most people understand what AI actually is. It isn't intelligence like humans or other mammals have. It's simply number crunching computing power, and as we all know, computers are garbage in and garbage out. Let's not forget that we put people on the moon w/o all this computing, and there is no substitute for human research and intelligence. AI is just a fad, something for people on the web to get "clicks" from.

Lots of people are always getting all hyped up every time some new thing appears online w/ tinnitus, but inner ear damage is inner ear damage, and neural pathways are neural pathways. There is no getting around that, and getting false hope is destructive. 20-30 years ago, when I got my tinnitus, I went to the American Tinnitus Association in Portland, Oregon, and their literature listed tinnitus as permanent and untreatable. To my knowledge, nothing has changed. We have masking and habituation, and that's great. That's real, and it helps many people.

 

Such an L take.

 

So Dr. Shore's clinical trials (University of Michigan) did not prove tinnitus is treatable?

 

My excitment over AI is less about the thought of some futuristic Jarvis that will start thinking for itself and coming up with the answer, but moreso the far superior technical 'thinking' ability than brain power and the ability to analytically use so much more data than the human mind can possibly deal with.

AI is being marketed out, partly as a fancy buzzword for quite simple computer systems taking input A, using built in logic and decision trees, and providing output B - but in partly by being able to interpret, extrapolate and see patterns in colossal amounts of data.

It will take collaborated effort and not researchers and scientists working away in ring fenced burrows - which is as big of an obstacle as the development of AI.

AI is already being used to take test results (e.g., scan results) and compare them against huge datasets of examples of other scans looking for intricate patterns and anomalies in a bid to reduce misdiagnosis - because the human brain is fallible and is unable to make the same analytical comparison with such vast datasets, or in as fast a time.

Of course crap in, crap out, but AI has the ability to go beyond, analyse in different ways, look beyond the thinking patterns us humans can.

It is this part of AI that I am more optimistic about without being unrealistic.

 

Tinnitus isn't necessarily permanent, as I've read many cases of spontaneous remission, even after years.

Still, I agree. AI is a waste of time, and tinnitus is a tough nut to crack. We seemingly have made real progress, however.