Inner Ear Hair Cell Regeneration — Maybe We Can Know More

"Their work identified several new genes that are controlled by these epigenetic switches in the inner ear that are crucial for the correct development of the cochlea and of hearing itself."

Do they really???

 

I don't know, but I want to know.

 

that's just what they published. do you really think they show all of their cards??? they've known how to regenerate cochlear tissues for years, now is the race to market.

 

I strongly believe it will.

 

In regards to the title of this thread,what more is there to know?

 

Otostem
https://cordis.europa.eu/project/rcn/110640/brief/en

 

I think about that sometimes. Being endlessly tortured while relief sits on a shelf somewhere in a lab 4000 miles away. Fuck life.

 

• Overall budget:
  
  € 7 892 595,60
  
  holy shit

 

Jeez, where are all these drugs at? Let’s get this show in the road.

 

7 million is if you deduct the overhead and setup costs almost nothing.

 

That's nothing in terms of medical research, it is a tiny budget.

That link you posted says that there is a risk of developing tumors as a result of the treatment, which is what I heard from a researcher on hearing cells regeneration at least 5 years ago:

"OTOSTEM developed protocols with morphogens or small molecule compounds that induce and determine otic cell fate. OPCs were tested for biological function and absence of tumorigenicity in various ex vivo and in vivo assays. Through comparison of OPC phenotype and gene expression, OTOSTEM partners identified native human stem cells as the stem cell source with the highest otic differentiation potential."

Time goes by and there is no significant progress, 5 years, 10 years, 20 years.. nothing.

 

FX-322 acts on LGR5+ stem cells. That is stem cell that express Leucine-rich repeat-containing G-protein coupled receptor 5.

https://en.wikipedia.org/wiki/LGR5

"Frequency is advancing the approach to develop a potentially restorative treatment for chronic noise-induced hearing loss. The paper titled, “Clonal Expansion of Lgr5-Positive Cells from Mammalian Cochlea and High-Purity Generation of Sensory Hair Cells,” is a cover feature in the journal Cell Reports, and can be accessed in the current online edition."

http://www.frequencytx.com/news-events/pr-02-21-2017.php

This video is from FrequencyTx
@1:08 They talk about the intestinal stem cells being able to regenerate.

Frequency Therapeutics

Intestinal epithelial stem cells are LGR5+.

"The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. It is currently believed that four to six crypt stem cells reside at the +4 position immediately above the Paneth cells in the small intestine; colon stem cells remain undefined. Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5, also known as Gpr49) was selected from a panel of intestinal Wnt target genes for its restricted crypt expression. "

https://www.nature.com/articles/nature06196

"Wnt Responsive Lgr5-Expressing Stem Cells Are Hair Cell Progenitors in the Cochlea"

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3417821/

That is how fx-322 works, by stimulating LGR5+ stem cells to proliferate.

Insulin Like Growth Factor-1 (IGF-1) also stimulates the proliferation of intestinal stem cells.

"IGF-1-enhanced epithelial cell migration by 2- to 2.5-fold after 12- and 24-hour treatment, respectively, the first step involved in gastrointestinal wound healing. Cell proliferation was significantly stimulated by IGF-1 as well."

https://www.ncbi.nlm.nih.gov/pubmed/10483904

IGF-1 is secreted by alpha granules from blood platelets. You can get platelet rich plasma from your own blood, and it is safe and unregulated by the FDA.

"The growth factors and other cytokines present in PRP include:[19][20]

• platelet-derived growth factor
• transforming growth factor beta
• fibroblast growth factor
• insulin-like growth factor 1
• insulin-like growth factor 2
• vascular endothelial growth factor
• epidermal growth factor
• Interleukin 8
• keratinocyte growth factor
• connective tissue growth factor "

https://en.wikipedia.org/wiki/Platelet-rich_plasma

These growth factors are what even causes wound healing in the body in the first place.

Another tissue that expresses LGR5+ stem cells are the olfactory sensory epithelium.

"Notch Signaling Regulates Lgr5+ Olfactory Epithelium Progenitor/Stem Cell Turnover and Mediates Recovery of Lesioned Olfactory Epithelium in Mouse Model."

https://www.ncbi.nlm.nih.gov/pubmed/29664186

PRP has been shown to regenerate loss of smelling called anosmia.

"After the third and finally the fourth therapy, 4 of 5 patients said that “their smell came back”, while the remaining one patient said that he could smell a lot but not everything. Until now none of them has lost again the recovered sensation of smell, so the results are long lasting."

http://www.tinnitusjournal.com/articles/anosmia-treatment-by-platelet-rich-plasma-injection.html

Oddly enough, that study was published in the International Tinnitus Journal.

Also, IGF-1 has been tested in human clinical trials to restore hearing loss and the publishers speculated that the action came from hair cell regeneration.

"Insulin-like growth factor 1: A novel treatment for the protection or regeneration of cochlear hair cells."

https://www.ncbi.nlm.nih.gov/pubmed/25937136

Also, I have received a PRP based treatment for my hearing loss and tinnitus and have experienced positive results, especially in my right ear. The doctor that treated me has also been using PRP to treat anosmia a full year before that study was published.

So to recap.
IGF-1 is in PRP.
IGF-1 causes LGR5+ cells in the intestine to proliferate.
PRP causes olfactory sensory cells, which are LGR5+, to proliferate.
The stem cells in our cochleas that we need to repair are also LGR5+.
IGF-1 has been shown to restore hearing possibly due to regeneration.

Here's more evidence that IGF-1 can achieve cochlear hair cell regeneration.

"Among these factors, IGF-1 promotes proliferation and survival of otic progenitor cells, supports neurogenesis and facilitates late differentiation in species from fish to humans"

https://www.researchgate.net/public...n_the_Progression_of_Age-Related_Hearing_Loss


-otic

adjective combining form
Definition of -otic (Entry 2 of 2)
: having (such) a relationship to the ear

https://www.merriam-webster.com/dictionary/-otic

 

You seem to have the most insight into this process out of anyone here.
Bottom line: When do you think this will be available?

 

I don't know if it ever will.

 

I thought FX-322 was going to be fast tracked. What happened?

 

They're holding over their last test results for a little while for some reason. They still may be getting fast tracked. They are just quiet right now.

 

JohnAdams grand theory on why mammalian hair cells don't regenerate.

They can regenerate. That's now an established fact.

The answer I think is blood. There is just not enough of the proteins involved in wound healing in cochlear fluid.

 

So are you less optimistic now that this is going to succeed? Its the middle of march and we all thought we would "hear" something by January.

I look through the articles daily to try and post something here, but it has been really quiet for a while. It would be nice to at least read about another breakthrough or something....anything. Not sure if we have hit a wall or these companies are just keeping quiet, but even the university articles that used to come out haven't given us anything lately.

 

No I think good things are happening.

 

Hi,
I think we should be optimistic due the fact, that there are several clinical trials for inner ear therapies running while we speak.
But all of them are proof of concept and won‘t likely cure hearing loss in a perfect way. Just inagine, maybe some people regain some hearing in 7-8 khz, maybe with 15 dB but maybe with some distortion or whatever, the drug would need much more testing to define treatment.
Don‘t get me wrong, I am waiting almost 15 years for some sort of cure, but I‘m afraid it won‘t that easy and fast.... but hopefully I am completly wrong.

 

Haven’t heard a peep out of Stanford in ages

 

They stepped back from their first visionary project "Cure Hearing Loss within 10 Years".
After that, they called, "Cure Hearing Loss within a Lifetime".
Once I read a statement, that they had to rethink their research approach, so they went in another direction
with different tools and as far I know with more Bioinformatics.
But they are still doing top notch research. I guess sooner or later they will publish something great again.

Most research is done in the Heller Lab
https://hellerlab.stanford.edu/

 

https://news.virginia.edu/content/u...AKzF4NZx6f2JdLkaUhX1kjUEBdLjfL8ch70-k0T1lIONw

Good article

 

https://www.actiononhearingloss.org.uk/live-well/our-community/our-blog/gene-therapy-breakthrough-for-hearing-loss/?utm_campaign=871315_Soundbite - March 2019&utm_medium=email&utm_source=Action on Hearing Loss formerly known as the Royal National Institute for Deaf People&dm_i=45UF,IOB7,14ZO5H,25RYF,1

Another article

"but even more crucially, administration of the same gene therapy after hearing onset in the mice was able to restore their hearing – and the mice were still able to hear 20 weeks later (mice live on average for 2 years). "

This is good news that fixing a bad gene actually restored hearing. I always thought that it would be too late, but this proved that is might not be.

 

But, people have had hearing loss and not had tinnitus (yet). I am one and many others here. So, if any study / medical treatment that is discovered can restore hearing even to an extent, it is a good question, is it not, whether it would cause tinnitus to lessen or even disappear?
If hearing loss is the culprit or a major culprit and you can restore it enough, I wonder if the brain can rewire itself ('hey, there's something there I can 'contact' again) so that there's no need to 'send' a buzzing sound in the head?

I dunno... I'm just rambling... :-/

 

Not everyone with a missing limb has phantom limb syndrome, not everyone with hearing loss has tinnitus.
Yes curing hearing loss will more then likely cause the brain to rewire itself, we see this in ear wax removal cases, middle ear surgeries, waiting for a damaged ear drum to heal, cochlea implants and even hearing aids.

The hyperactive neurons in the auditory brain must have the potential to reorganize and associate with auditory nervous tissue if hair cells and synapses (or anything else) is restored.

 

but does everyone with hearing loss due to acoustic trauma have shitnitus?

 

No.

It also sometimes fades (brain filters out tinnitus perception)

 

I think it’s rare-we aren’t talking age related, genetic etc. How often does someone with hearing loss due to acoustic trauma actually not have tinnitus? I’m talking measurable permanent hearing loss after say a blast injury, this kind of injury happens with no tinnitus? I have no idea, but I’ve never heard of a major trauma including permanent hearing loss with no tinnitus to follow.

 

Hearing loss by itself may or may not give you tinnitus. Anxiety is one of the triggers. There are so many factors... For most people just putting a hearing aid in will drop tinnitus levels within seconds or minutes. The brain can rewire itself. I had hearing loss with hearing aides and that kept tinnitus away for many years until the hearing aides couldn't compensate anymore and I had anxiety.