Inner Ear Hair Cell Regeneration — Maybe We Can Know More

I can try this when I will finish with Lyme if there isn't improvement with my hearing after that. We should be careful with MAOi and other things like that when trying new things.

Appropriate dosage is unknown, but the most common dosage is 10-30 mg per day.

There is an apparent lack of human studies. Side effects are unknown.

However, users report:

• Overstimulation
• Restlessness
• Dizziness
• Nausea
• Irritability
• Trouble sleeping

Possible drug interactions of 7,8-Dihydroxyflavone are unknown.​

 

fun!

 

What should we do?

Curcumin at least is curing my ear tinnitus but there is also somatic part of tinnitus that is not changing and I want my hearing back.

I belive that Mother Nature gave us everything what we need in substances contained in plants and herbs but people are stupid and for centuries were burning and hanging people who were living in forests, educating themselves and increasing their knowledge about plants and interactions with them. This all knowledge is now forgotten and delayed and phytoteraphy is not even academic subject.

In Poland we have only few professors who made herbal treatment their work f.ex dr Różański http://rozanski.li/ who is truly and scientifically exploring plants. It's really tragic that people lost that way.

 

yep. hey I am right there with you brother. I ordered some 7,9 dihydroxyflavone today. its plant derived. maybe we are cutting edge science dudes, maybe I am an idiot. poop.

 

Following this very closely. Let us know if you get any improvements.

 

This is interesting:

This paper induced me to think that curcumin by itself WONT regenerate hair cells, which may be true. However, this paper seems to throw in mention of curcumin just for the sake of saying it wont allow atoh1 to accumulate, which is necessary for HC regeneration.
Bear in mind, DAPT is a very expensive lab chemical that functions much like ly411575, and DAPT is being researched by big pharma to use for curing hearing loss.

"Furthermore, inhibition of histone acetyltransferase (HAT) activity by curcumin partially blocks the DAPT-induced accumulation of Atoh1 mRNA, further indicating a need for ongoing histone acetylation to induce Atoh1 (Fig. 6B). Curcumin, either on its own or in conjunction with DAPT, had no effect on the expression level of the Notch effectors Hes5 and Hey1 (data not shown)"

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4813338/
data not shown? That's funny because these other two papers state the opposite, that curcumin reduces the levels of these genes:

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:
"The expression of Notch-1, Hes-1, Hey-1 and Hey-2 genes at the mRNA levels was downregulated after curcumin treatment."
https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1742-4658.2012.08607.x



If this paper is true then doctors should be telling test subjects to not take curcumin while they are given drugs to regenerate their hair cells.

 

All the assumption of the idea with the regeneration of hair cells in humans by manipulation with supporting cells (progenitor cells) is based on the well-known fact of the possibility of spontaneous regeneration of hair cells by vertebral non-mammals, amphibians, and so on.

Repeated laboratory tests were performed in which the internal cells of chickens or other birds were destroyed with ototoxic drugs or loud noise, then within 2 weeks the researchers observed spontaneous regeneration of hair cells and positive dynamics of otoacoustic emission.

This was clearly demonstrated by the role of precursor cells of the inner ear.

However, according to the data that I have today, the cells in birds have not regenerated to an ideal initial state. There were some defects in synaptic connections and neuronal processing. That is, the rumor was hearing not returning by 100%, but, say, 95%.

This causes fear.

Since many here have very little damage, which is still a trigger in modulating tinnitus, it can be assumed that only a full return of the ideal functionality of the inner ear can completely suppress the manifestations of tinnitus.

You see, the cells regenerate, but there is some failure in synaptic-neural connections in birds.

 

But do you know how much hearing loss the birds initially acquired?

 

I don't think your assumption is justified. Rather, it's probable that repair occurs in proportion to damage, not in an absolute measure. So, had the birds only sustained minor damage, too 95% of that damage would have repaired.
Also - unlike birds, treatments may be capable of repeated application.
Of course, all this too is just speculation.

 

Also stop scaring me lol

 

I don't think it is reasonable to expect that tinnitus will completely disappear with hair cell regeneration. Hair cell regeneration will simply not be perfect at the beginning. However there's good hope to expect a reduction in the volume, which would also be very helpful.

 

We’ll just have to be patient.

I do think that 95% of hearing restoration in any particular frequency may be enough to quiet tinnitus. In fact I do think most people suffer some* hearing loss... but it’s only after a certain amount of damage that the brain compensates and turns up the volume.

What I am more afraid of is that regenerated hair cells will pick up sound but send it it the brain all garbled and twisted. And that’s a possible reason why mammals evolved with this feature turned off by default.

But that’s all speculation at this point. We’ll have to let FX and co experiment.

 

Also - many people report reduction or even complete cessation of T with hearing aids even though hearing aids do not restore auditory perception to the degree of natural healthy hearing.

 

Read this article and tell us about your impressions.
https://www.scientificamerican.com/article/a-40-year-quest-uncovers-hearings-holy-grail-protein/

 

Yes! Excellent! This confirms what I am saying in my post: there’s more to (correct) hearing than just hair cells.

Hair cell regeneration is one part, making sure these cells work properly is another and could require application of this protein... and who knows what else...

But now we’re talking about actually restoring hearing... maybe for tinnitus to decrease or go away... we do not need to get our hearing completely restored. Regenerating some of it, may already have some effect.

I just hope all research teams share their findings openly and other teams connect all the necessary dots in search of an comprehensive approach.

Hair cell regeneration (and afterwards perfecting that practice) remains a first and important step.

 

I can confirm this! A few months ago there was a big story in the newspaper and TV in my country that even the insurance had to pay a T sufferer a hearing aid because of a reduction of the T while using hearing aids. Because no other treatment helped the patient went to the court against the official insurance and won. That was big news. I think it also showed the need of a cure.

Thats also why I hope insurance will force for a drug-based cure because if all T sufferers try to get the hearing aid payed and a lot of service around it over years it might be cheaper to make a cure. fingers crossed

 

Do any of you have access to ResearchGate.net?

It is of benefit to download this article and familiarize ourselves with it -

https://www.researchgate.net/public...view_Inner_Ear_Stem_Cells-An_Oxymoron_but_Why

Thank you.

 

Is Tmc1 the “holy grail” protein for ear hair functionality?

 

I don’t remembered who posted it but I recently found. I was looking through McLean’s actual research papers and I found some more indications that they replicate as well

 

Lecture: Toward a True Cure for Hearing...

Watch 15-20 he pulls up the chart and explains Lgr5 and how it will expand and close broken areas. If you wanna check out his full research article I’ll post it, just ask. He has done a TON of work over the last few years and it takes a minute to get through so if you need a good summary, I’m your guy.

 

I almost lost the link so I’m going to post it anyway.
http://dev.biologists.org/content/143/23/4381

 

Lgr5 doesnt expand. It is the presence of the protein lgr5 in the supporting stem cells that is a marker showing that notch inhibition/wnt activation will cause them to differentiate into functioning cilia (hair cells). Lrg5+ (positive) just indicates that the cells express that protein. Not trying to be a smartass, I've just studied this into oblivion trying to do this myself.

 

No it’s cool. I’m just trying to figure it out myself.

 

https://www.healtheuropa.eu/treatment-for-deafness/88286/

Could hair cell regeneration be a treatment for deafness?
28th September 2018

A treatment for deafness could be on the horizon, as a European study investigates the possibility of inducing regeneration of the inner ear cells.
Researchers have proposed to use embryonic stem cells as a platform for in vitro inner ear studies to potentially be a treatment for deafness. Deafness due to disease, ageing, or birth defects is caused by the loss of hair cells in the inner ear, which is the structure responsible for the detection of equilibrium and sound. Currently, deafness is a progressive and irreversible condition in humans, with the typical treatment to be the use of hearing aids.

Utilising hair cells from stem cells.
Dr Andrew Jarman, project coordinator, explains: “our approach relies on a different methodology that allows for the first time, the production of large numbers of hair cells. ″

The scientists of the EU fundedGRNHairCell project proposed to use embryonic stem cells (ESCs) as a platform for in vitro inner ear studies. ESCs establish an alternative and powerful approach to, generate unlimited numbers of hair cells in a simple culture dish without the use of animals.

Dr Aida Costa, who performed the work, used the three proteins which control the hair cell development in the embryo – Atoh1, Pou4f3 and Gfi1.

Through genetic manipulation of ESCs to activate expression of these transcriptional regulators, a direct and robust conversion of stem cells into a hair cell phenotype was successfully achieved. “A simple in vitro culture system gave us the opportunity to investigate how these proteins work together in a network to induce the formation of hair cells.” Said Costa.

Using the in vitro culture system, researchers were able to provide vital insight into the dynamics of hair cell regeneration. Atoh1 had been the main protein undergoing intense research, as it is a key player in identifying the regeneration of lost hair cells in patients with deafness. However, Atoh1 demonstrated limited regenerative capacity, indicating that other factors are implicated in the process. During the GRNHairCell study, Dr Costa identified Gfi1 as a switch to hair cell commitment and a contributor to Atoh1 transcriptional activity. Moreover, analysis of gene expression and protein-DNA binding activity unveiled important information on the function of these regulatory factors.

What is the clinical significance?
The molecular structure in which Gfi1 is able to change Atoh1 and Pou4f3 transcriptional activity is most definitely of great scientific importance. Costa highlights the fact that from a clinical perspective “it is also important to test this particular combination of transcription factors in animals with damaged inner ears to see if we can reverse the damage. ″

Jarman concludes: “although there may be no immediate clinical application of the GRNHairCell study results, the gained knowledge brings us a step closer to comprehending the process of inner ear development and exploiting it in the therapy of deafness.

Identifying the key aspects in hair cell regeneration could potentially lead scientists to establish therapeutic approaches and even find a treatment for deafness.

 

Hi, is the REGAIN Audion trial still going ahead. I haven't read anything about it lately.

Sorry if this has been answered elsewhere.
Thank you.

 

Dont embryonic stem cells come from dead babies?

 

The embryos being used in embryonic stem cell research come from eggs that were fertilized at in vitro fertilization clinics but never implanted in a woman's uterus. The stem cells are donated with informed consent from donors.

 

@JohnAdams : I immediately asked myself the same question (or babies designed for these specific therapeutic reasons). In this sense, the laws on bioethics differ according to the country.

 

I still think Frequency Therapeutics' FX-322 is our best bet for restoring hearing. Stem cell treatment is probably a decade away.

 

There are members on this forum that have hade successful stem cell treatments. The first one did it 5 years ago.