Cochlea-Targeted Delivery of a Neurotrophic Agent as a Strategy for the Treatment of Hearing Loss

Connecting hearing helper molecules to the ear bone
“Bisphosphonate-Linked TrkB Agonist: Cochlea-Targeted Delivery of a Neurotrophic Agent as a Strategy for the Treatment of Hearing Loss”
Bioconjugate Chemistry

Hearing loss is a common affliction associated with advancing age and exposure to very loud noises, affecting two-thirds of adults over age 70. But living with hearing loss may not be inevitable. Scientists report in the ACS journal Bioconjugate Chemistry a novel approach to the restoration of hearing that delivers stimulants of cell growth and connectivity directly to damaged ear cells.

Hearing loss is attributed to the degradation of specialized inner ear cells, including hair cells and spiral ganglion neurons, as well as the connections between these cells. These cells are located within the cochlea, the shell-shaped ear bone that orchestrates hearing. Loss of synapses between these cells because of loud noises or aging can lead to “hidden hearing loss,” or difficulty hearing in a noisy environment. It may also lead to the development of tinnitus, or “ringing in the ears.” Biological molecules called neurotrophins are involved in the development and proper wiring of hearing cells. This raises the possibility that delivering molecules, such as 7,8-dihydroxyflavone (DHF), that mimic neurotrophin activity, to the inner ear could bring the damaged cells back into auditory action. Delivery is an issue though, as therapeutic molecules tend to be quickly flushed out by inner ear fluids. So, David H. Jung, Charles E. McKenna and colleagues wanted to see whether tethering DHF to another molecule, one that sticks to bone, could anchor the therapeutic activity to the cochlea long enough to potentially restore hearing.

The researchers designed and synthesized a molecule combining DHF and bisphosphonate, which latches onto bone, then tested its neurotrophic activity. In cell cultures, the combo molecule bound bone mineral, while maintaining the ability to stimulate spiral ganglion neuron outgrowth. This new molecule also regenerated synapses in mouse inner ear tissue that had been damaged. Future work will test the potential of the molecule in animal models of hearing loss.

The authors acknowledge funding from the American Academy of Otolaryngology-Head and Neck Surgery Herbert Silverstein Otology and Neurotology Research Award, the American Otological Society Research Grantand by a grant from the National Institute on Deafness and other Communication Disorders.

Note: ACS does not conduct research, but publishes and publicizes peer-reviewed scientific studies.

 

This was already posted: https://www.tinnitustalk.com/thread...be-we-can-know-more.3131/page-120#post-323583 including a nice non-technical description: https://www.tinnitustalk.com/thread...be-we-can-know-more.3131/page-120#post-323636

 

Anyone seen this video on small molecule research.

Part of what they are talking about sounds similar to Frequency Therapeutics...

New research could help fix hearing loss

 

No they are repairing synaptic connections (auditory nerve to hair cell), Frequency is generating new hair cells entirely.

The way I see it both are needed most likely.

 

the year is 2023 Frequency Therapeutics fails clinical trials for not parting with these guys or vice versa.

 

I emailed Mr. Jeff Karp sometime ago and asked this:

"But I would like to ask you if your method will also repair/regenerate the auditory nerve/connections from nerve to hair cell?"

Mr Jeff Karp responded:

"Thank you for the note - we have some evidence to suggest the answer to that question is yes - but only time will tell as we push things forward

with warm regards,
Jeff"

 

Assuming Jeff Karp is at Frequency, maybe someone could email Jeff and let them know about these guys. Perhaps they could fund their research in return for use of their results or something.

 

THEY HAVE SOME EVIDENCE

 

It's a proof of concept and still a long time away.

https://news.usc.edu/140224/new-study-shows-hope-for-hearing-loss/

The lab study, conducted by scientists at USC and Harvard University, demonstrates a novel way for a drug to zero in on damaged nerves and cells inside the ear. It’s a potential remedy for a problem that afflicts two-thirds of people over 70 years and 17 percent of all adults in the United States.



The researchers designed a molecule combining 7,8-dihydroxyflavone, which mimics a protein critical for development and function of the nervous system, and bisphosphonate, a type of drug that sticks to bones. The pairing of the two delivered the breakthrough solution, the researchers said, as neurons responded to the molecule, regenerating synapses in mouse ear tissue that led to repair of the hair cells and neurons, which are essential to hearing.

Hidden hearing loss:
Hearing loss is projected to increase as the U.S. population ages. Previous research has shown that hearing loss is expected to nearly double in 40 years. Damage to the inner ear can lead to “hidden hearing loss,” which is difficulty hearing whispers and soft sounds, especially in noisy places. The new research gives hope to many hoping to avoid loss of hearing and quality of life.
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From what I understand researchers have figured out how to get a drug to bind to the hard bone around the cochlea to access damaged aspects of the auditory nerve, repairing cochlear synapse damage.

Why would this help tinnitus you may ask?
https://www.tinnitustalk.com/threads/inner-ear-hair-cell-regeneration-—-maybe-we-can-know-more.3131/page-127#post-360596
Statistics on reversing hearing loss reducing tinnitus.

A growing body of evidence suggest tinnitus is in a larger category of neurological conditions relating to "phantom input". Take the most common example of phantom limb pain.

I subscribe to the most widely accepted hypothesis that states the brain fills in a gap for hearing loss and has a gateway mechanism, just as the brain fills in phantom gaps for other conditions, and I encourage you to research the topics for yourself and draw your own conclusion.
https://www.livescience.com/27641-phantom-pain-linked-to-brain-mapping.html

https://www.google.com/search?q=tinnitus+phantom+pain
https://www.google.com/search?q=central+gain+tinnitus


So yes, let's hope this ends up as a promising method of deliver and treatments for hearing loss and tinnitus and who knows what other applications in the future. The future looks bright!

 

Gee we just used a commercially available drug to restore and repair inner hair cells. Let's sit on our asses for years and wait for big pharma to ante up the cash needed for FDA testing of this stuff while people continue to suffer instead of getting it out ASAP.

 

Yep, thats pretty much how it works. I wish Decibel or Frequency would jump on this.

 

I honestly dont think anyone will because 7,8 dihydroxyflavone isnt a proprietary drug and is already available commercially. Where is the profit in that? I doubt we will ever "hear" anything about this stuff ever again. I've actually already ordered some but I doubt taking it orally will do anything. We'll probably have to go to another country to get something like this.

 

If it is a straight forward procedure maybe a clinic could offer this service or even a doctors office. I'm sure lots of people would pay good money to have this done. Yeah, I don't think just taking it orally will do anything by itself. They mention it was the combination of the 7,8-dihydroxyflavone and the bisphosphonate that made it work.

 

It has to go through FDA clinical trials which cost a bazillion dollars!
Heres the potential cure for all of us right now:

7,8 dihydroxyflavone + bisphosphonate + a syringe


You can buy 7,8 dihydroxyflavone:
http://nootropicsdepot.com/7-8-dihy...MI1f7bxKPU3QIVlMDICh3OQwNVEAkYASABEgIspPD_BwE
$24.99

You can buy bisphosphonate:
https://m.goodrx.com/bisphosphonates
$10.02 (fosamax)

You can buy a syringe:
https://liquidationsoutlet.com/prod...ge-with-21g-x-1-precisionglide-needle-qty-50/
$14.99

THATS $50 FOR A POTENTIAL CURE!!!!!!!!!!!!!!!!!!!! AND THATS PROBABLY ENOUGH FOR 5 OR MORE PEOPLE. AAAAAAAHHHHHH
IVE SPENT HUNDREDS AND HUNDREDS OF DOLLARS ON CBD OIL AND SUPPLEMENTS.

But noooooooo we'll have to wait for f**king ever while we go insane and our lives fall apart because of effing capitalism and stupid ass rules.

God help us.

 

@JohnAdams are you going to inject somewhere 7,8 dihydroxyflavone?

 

Wow thats really amazing news thanks for sharing.

Again a new method to deliver drugs to the inner ear. The easier we can reach the cochlea the better treatments will come I hope.

 

It wasnt just a drug delivery method. It repaired nerves and HAIR CELLS.

 

technically they could borrow this method.

I hope they do infact experiment with it.

Frequency shouldn't fail a trial if their method of accessing the cochlea doesn't work and should be able to try alternative methods.

 

I also think that the access is important there is no doubt companies will regrow something in the inner ear ... they just started to use different types of drugs in vitro on the cochlea and its getting faster and faster. I will look at that drug again when they made tests in living creatures at that time it gets interesting for me.

This method allows maybe to deliver a drug to the cochlea over a long period of time without any stress for the patient to have a full potential of the drug or to use a higher dose.

Maybe Frequencies approach works but the drug delivery method will fail or people with a lot of hearing loss need 10-20 or more times the treatment (injection eardrum). This could maybe help.

 

I know some herbal ointments that can get inside bones so maybe we can try this way.

 

Dude if that fx322 can get into mice cochleas then it should definitely get into human ones.

 

What about existing hair cells that still have damaged synaptic connections?

 

Cure for ear bones, muscles, nerves, ear drum, cochlea, hair cells. We need fx 322 and all the possible treatments to get cured.

 

nope.

the article you posted said the 7,8 DHF repaired the hair cells.

I'm just going to have to dress up like a damn mouse and sneak into one of these labs where they are testing this stuff. ​

 

I agree with that the way clinical trials go about are largely burdensome.

But still I'd be more confident if it worked on the cochlea of a living primate and not a dead rodent
however it is much better to make sure double blind +placebo measured human studies are done.

I just criticize the FDA for being too slow.

 

This is why only proprietary drugs that can be sold for a large profit margin can be FDA approved for certain use:

According to a 2014 study by the Tufts Center for the Study of Drug Development (TCSDD), the cost of developing a new drug, from research and development (R&D) to marketing approval, is approximately $2.9 billion. This includes actual out-of-pocket costs averaging $1.4 billion, opportunity costs of nearly $1.2 billion, and the cost of post-approval studies amounting to $312 million.
https://www.liaison.com/blog/2017/05/02/cost-drug-development/

People, this means that we will never have legal 7,8 DHF ear injections, even if it would save our asses.

Why would a company invest $2.9 Billion to approve a drug that, once approved, anyone ENT can just make themselves for $0 a dose and can't be patented?

If no patent, no cure. No natural plant based cures. No cheap cures. Let that sink in.

This means that we may actually have a better chance at doing this ourselves.

It is the government that is standing in the way of a cure.

 

This is why i have little faith in a cure in my life time because this world is upside down, back to front and inside out. Even with a proven cure right there sitting on the shelf i still wouldn't have that much hope because of all the red tape in this world. Profit always comes before people in this world and i cant stand it personally.

 

Nobody has to wait for the FDA.

Hypothetically, one could synthesize the solution along with the correct dosage all that would be needed is the gel and an ENT manual for giving shots into the ear canal.

Of course nobody would be able to sell the solution or patent it and they would need full liability signed away for treatments...

Let me guess... Not legal and highly unethical?

 

post like these can literally cause me to have panic attacks and consider suicide.
I cannot go the rest of my life with comprised hearing only expected to get worse.

 

I know a chemist that would be able to give easy instructions on how to get it done. Question is, does somebody here know more about the gel that disburses after use (e.g., Frequency Therapeutics)?

Also answering my own question: no, it is not legal to test upon human subjects without applying for approval by the FDA and there are punishments for not doing so. Which means the only human subject without FDA approval is yourself...