Inner Ear Hair Cell Regeneration — Maybe We Can Know More

Did you just make that up? They are already in phase 2 human trials with this stuff.

 

They didn't even mention a gateway mechanism hypothesis or factors like GABA playing a role.

Some hypothesis suggest everyone with hearing loss has hyper neuronal activity in the DCN, but it is only perceived consciously in smaller groups. (tinnitus sufferers)

it's like they just want people to feel hopeless, and i love how they never mention if curing hearing loss will also cure tinnitus.

 

Researchers need you contrast.

 

No, it is a conversation I had like 5 years ago. I hope scientists find something to repair hearing and conditions like hyperacusis. I imagine there must be several companies and labs researching this, maybe some of them are successful in the end.

 

As you read research, have you noticed how they are desperate for funding all the time (our tax money). Can you imagine the fear it would cause if the tinnitus community targeted a lab that is wasting resources to have their funding cut off. We could show them that we are a threat to them and they would have t0 pay attention. It would scare other labs in the same field.

 

Finding a cure would end tax dollar funding.

 

demanding a cure for sensori-neural hearing loss is one good meme.

 

The only thing a bully respects is a bigger bully. I can only imagine the human suffering that has passed through here, I am merely offering the idea as an example, we vastly outnumber them and this numerical advantage has not been played well. We donate here and there, but really, what are we "actually" donating to? Someone mentioned Rivolta earlier, that chap is having a laugh with his "es cell" nonsense. Its not about cellular repair, its about cash in his pocket. I don't really see the point in action on hearing loss funding him anymore, why not give some money to a younger lab.

 

Tell me where I should donate, or support?

 

I am not here to tell you where to donate, that is a personal thing for you to investigate, I am just pointing out, that it may be much more effective to target the boards (eg the NIH grant board) that give these researchers money, its FREE money guys! Someone is taking the piss. C'mon, its only when private money arrived on the scene that some movement was made, these "leeches" need to be singled out, if we can just rock a few boats, think of the fear it would instill for other freeloaders thinking of pissing grant/charity money into the wind. I am not suggesting its only r&d, but charity and clinicians themselves have their nose in the trough for their own benefit.

 

Sadly I agree. The pursuit of money is far greater than the desire for a cure. Big pharma and medical device manufacturers are profit driven companies that utilize healthcare, not healthcare driven companies that utilize profits, grants and donations.

Basically I feel this way regarding tinnitus. My ENT does surgery on many children with severe health issues. Thank God for these doctors.

T has made me a bit cynical? haha

 

Regrowth of cochlear hair cells is not only associated with notch1 inhibition but also decreased levels of the genes
Hes1, Hes5, Hey1, HeyL, and Jagged1.


"Expression changes of genes in the Notch pathway were measured using immunostaining and in situ hybridization, with most changes observed in the apical one-third of the cochlea where the majority of HC regeneration occurs. Expression of the Notch target genes Hes1, Hes5, Hey1, HeyL, and Jagged1 were decreased."

https://www.frontiersin.org/articles/10.3389/fncel.2018.00120/full

Hes1:
"Treatment with curcumin resulted in downregulation of Notch1 and its downstream target, Hes1"

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5517797/

Hes5:
"Curcumin, isolated from Turmeric, inhibits the development of pulmonary arterial hypertension via down regulation of Notch3 and its target gene Hes-5"

https://genomediscovery.org/2017/08...arterial-hypertension-via-down-regulation-of/

Hey1:
Compared with control, there was a reduction of Notch-1, Hes-1, Hey-1 and Hey-2 mRNA levels after curcumin
treatment, suggesting that curcumin resulted in the transcriptional inactivation of Notch-1 signaling pathway"

https://www.google.com/url?sa=t&sou...FjADegQICBAB&usg=AOvVaw0qrRfrpFI6A27pclNWUqnE

HeyL:
No data. Maybe someone can help me find this.

Jagged1:
"Our studies demonstrate that curcumin inhibits the expression of Jagged-1 and the Notch-1 receptor. Curcumin also inhibits γ-secretase complex proteins, thereby inhibiting cleavage of the Notch receptor."

https://www.google.com/amp/s/www.re...f-Jagged-1-and-the-Notch-1_fig8_221859732/amp

The drug that induces hair cell regeneration is a gamma (γ) secretase inhibitor.

"LY411575 is a potent γ-secretase inhibitor"

http://www.selleckchem.com/products/ly-411575.html

 

Recent Advancements in the Regeneration of Auditory Hair Cells and Hearing Restoration

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5534485/

 

Wow this is very interesting ! This would mean that curcumin is a great spice for Cochlear repair? It sounds really really cool !

 

Hypothetically. I'm trying and it is a very safe so why not at least try. I wish some lab would publish research on it.

 

Is your T still at manageable level? I just started my curcumin supp. today. I know it will take a long time to see any benefit, if any.

 

Wow how cool. Probably dose is the thing to matter, maybe funding some research for them to investigate and make a trial could be cool.

 

not sure yet.

I started mixing a tablespoon of butter, a half a tablespoon of pepper, and 4-5 grams of curcumin powder and it's actually quite tasty. I just waiting for someone to give me a valid reason why this wont work.

 

I don¨t want to crash your party, but the problem is that it´s got an extremely low bio-availability.
Swallowing 3-4 grams, will hardly show any concentration in your bloodstream.
We need it to get administered where it hurts!

Sorry to be a wise-ass, but thats what I just red(In a norwegian article)
Still, I´m gonna buy it for myself.

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1434783/ I think 5g is a small dose

 

"The Lgr5-expressing cells differentiate into hair cells in high yield. From a single mouse cochlea, we obtained over 11,500 hair cells, compared to less than 200 in the absence of induction. The newly generated hair cells have bundles and molecular machinery for transduction, synapse formation, and specialized hair cell activity. Targeting supporting cells capable of proliferation and cochlear hair cell replacement could lead to the discovery of hearing loss treatments."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5395286/

"n-3 PUFA+curcumin synergistically increased targeted apoptosis in DNA-damaged Lgr5+ stem cells by 4.5-fold compared with control at 12 h and maximally reduced damaged Lgr5+ stem cells at 24 h, down to the level observed in saline-treated mice. Finally, RNAseq analysis indicated that p53 signaling in Lgr5+ stem cells from mice exposed to AOM was uniquely upregulated only following n-3 PUFA+curcumin cotreatment. These novel findings demonstrate that Lgr5+ stem cells are uniquely responsive to external dietary cues following the induction of DNA damage, providing a therapeutic strategy for eliminating damaged Lgr5+ stem cells to reduce colon cancer initiation."
https://www.ncbi.nlm.nih.gov/m/pubmed/27831561/

Very interesting.

 

You're so wrong. You can increase the bio availability by ingesting it with animal fat and pepper. Please tell me I'm wrong.

I turned my hands and feet yellow. It's in my blood. It's okay. I'm experimenting. I will know soon enough whether I'm right or wrong.

 

It is. That is the awesome part about this small molecule substance. It is very very pungent yellow. Therefore if your hands and feet are yellow then you know it is in your blood stream. Seems like some freak plant.

 

If this works. I will shit bricks of yellow. Still got pick me up some though

 

Bricks of yellow gold.

 

I think what's needed is a look at hearing loss rates in India where they eat curcumin by the boatload.

 

WOW n-3 PUFA!! that's fish oil!!!!!

The cochlear cells are lgr5+ so I wonder if taking fish oil with the curcumin will help repair the damaged cochlear cells as well as regrow new ones.

 

way ahead of you.

 

N-3 PUFA is fish oil? So N-3 PUFA is omega-3 fatty acids?

I've had success taking fish oil capsules to help with depression. No doubt about its effectiveness. I would take up to 12 capsules a day. If I remember correctly it helps the brain. (haha, I can't remember) ... myelin sheath, this is what it helps repair, neurons. So now this is making some sense.

 

As I see curcumine and n-3 PUFA are healing DNA damaged Lgr5 cells and making them working normal. To regenerate colchea we have to make them to work abnormally because some regeneration mechanisms are switched off in mammals. I think thats a problem I had read before that regenerating colchea with markers inhibitors is possible but it is also a cancer risk.