MemberI've been in S. Korea for the last 2 weeks getting PRP injected into my ears at Dr. Shim's Solsaem clinic in Seoul. I will answer your questions as well as periodically update my status. I've got between 2 and 3 months for the full effects to manifest.
Here's how I think Minbo Shim's therapy works. He didn't explain this to me, I put all of this together myself.
First off, this is how hair cell regeneration technology works.
A class of chemicals called notch inhibitors or gamma secretase inhibitors makes contact with the surface of the stem cell. The stem cells in our inner ear are classified as LGR5+ (positive), meaning that it expresses a gene called Leucine-rich repeat-containing G-protein coupled receptor 5.
https://en.wikipedia.org/wiki/LGR5
Inside the cell there is a protein called Beta-Catenin. This is the finger that throws the "switch" that makes LGR5+ stem cells proliferate, which means divide and regenerate into mature cells, in this case, hair cells in the cochlea. In order for this to occur, enough Beta-Catenin has to enter into the nucleus of the cell.
But, the reason our hair cells aren't regenerating on their own is because once Beta-Catenin is created inside the cell, there is a group of proteins that form something called the Beta-Catenin destruction complex, this destroys the Beta-Catenin before it can enter into the nucleus in enough quantity to activate the proliferation process.
The β-catenin destruction complex.
https://www.ncbi.nlm.nih.gov/pubmed/23169527
One way to stop the Beta-Catenin from being destroyed is by activating a cellular signalling pathway called WNT (pronounced wint).
Generation of hair cells in neonatal mice by β-catenin overexpression in Lgr5-positive cochlear progenitors.
https://www.ncbi.nlm.nih.gov/pubmed/23918377
This is how drugs like FX-322 work to "wake up" dormant stem cells in the inner ear.
There is a class of proteins involved with many functions in our bodies called growth factors.
One of these growth factors is called insulin-like growth factor 1. IGF-1.
IGF-1 has been shown in multiple human clinical trials to improve hearing recovery.
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
Actually I never noticed this part before but they verified that it causes cochlear supporting cells to proliferate in cochlear explants.
"The mechanisms of IGF1-induced maintenance of hair cell number have been investigated using a cochlear explant culture system, which demonstrated that IGF1 acts on supporting cells, leading to the inhibition of hair cell apoptosis and the proliferation of supporting cells."
Another study, showed that IGF-1 increases cellular Beta-Catenin levels.
Insulin and IGF-1 stimulate the β-catenin pathway through two signalling cascades involving GSK-3β inhibition and Ras activation
https://www.nature.com/articles/1204064
"IGF-1 increased the cytoplasmic levels of β-catenin."
IGF-1 is produced in our bodies, in part in blood platelets.
There is not any blood in our inner ear fluid. Inner ear fluid is different from blood.
https://en.wikipedia.org/wiki/Endolymph
You can create a platelet rich composition of blood by putting drawn blood in a centrifuge which separates the platelets into something called platelet rich plasma, PRP.
PRP contains growth factors, including IGF-1.
The growth factors and other cytokines present in PRP include:
In your middle ear there is a semi-permeable membrane called the round window.
https://en.wikipedia.org/wiki/Round_window
So that's how you can deliver medicine to the cochlea, by filling up the middle ear, via eardrum injection, with a viscous solution containing X substance, it rests in the middle ear and the substance, if molecularly small enough, will diffuse through the round window membrane. That's why the various presentations produced by FrequencyTX, as well as their homepage emphasize that their products are "small molecule drugs", because this is exactly how FX-322 is delivered to the cochlea.
Other neurotrophic compounds are also being investigated to repair lost cochlear synapses by diffusion through the round window membrane.
Round-window delivery of neurotrophin 3 regenerates cochlear synapses after acoustic overexposure
https://www.researchgate.net/public...cochlear_synapses_after_acoustic_overexposure
So that's my theory, that IGF-1 works just like FX-322 to disable the Beta-Catenin destruction complex and cause the stem cells to proliferate into functioning hair cells except that IGF-1 is already produced in our bodies and needs to be manually introduced into the cochlea. Also PRP may be much safer than FX-322 because it is good for healing holes to the eardrum that would be caused by the injection.
Topical use of autologous platelet rich plasma in myringoplasty.
https://www.ncbi.nlm.nih.gov/pubmed/25794691
"Topical autologous PRP application during myringoplasty is safe and highly efficient and successful with no reported complication"
https://www.ncbi.nlm.nih.gov/pubmed/25794691
Now watch the nay-sayers purposefully push this post up the page with extremely long-winded ad-hominem attacks on me and Minbo Shim.
Here's how I think Minbo Shim's therapy works. He didn't explain this to me, I put all of this together myself.
First off, this is how hair cell regeneration technology works.
A class of chemicals called notch inhibitors or gamma secretase inhibitors makes contact with the surface of the stem cell. The stem cells in our inner ear are classified as LGR5+ (positive), meaning that it expresses a gene called Leucine-rich repeat-containing G-protein coupled receptor 5.
https://en.wikipedia.org/wiki/LGR5
Inside the cell there is a protein called Beta-Catenin. This is the finger that throws the "switch" that makes LGR5+ stem cells proliferate, which means divide and regenerate into mature cells, in this case, hair cells in the cochlea. In order for this to occur, enough Beta-Catenin has to enter into the nucleus of the cell.
But, the reason our hair cells aren't regenerating on their own is because once Beta-Catenin is created inside the cell, there is a group of proteins that form something called the Beta-Catenin destruction complex, this destroys the Beta-Catenin before it can enter into the nucleus in enough quantity to activate the proliferation process.
The β-catenin destruction complex.
https://www.ncbi.nlm.nih.gov/pubmed/23169527
One way to stop the Beta-Catenin from being destroyed is by activating a cellular signalling pathway called WNT (pronounced wint).
Generation of hair cells in neonatal mice by β-catenin overexpression in Lgr5-positive cochlear progenitors.
https://www.ncbi.nlm.nih.gov/pubmed/23918377
This is how drugs like FX-322 work to "wake up" dormant stem cells in the inner ear.
There is a class of proteins involved with many functions in our bodies called growth factors.
One of these growth factors is called insulin-like growth factor 1. IGF-1.
IGF-1 has been shown in multiple human clinical trials to improve hearing recovery.
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
Actually I never noticed this part before but they verified that it causes cochlear supporting cells to proliferate in cochlear explants.
"The mechanisms of IGF1-induced maintenance of hair cell number have been investigated using a cochlear explant culture system, which demonstrated that IGF1 acts on supporting cells, leading to the inhibition of hair cell apoptosis and the proliferation of supporting cells."
Another study, showed that IGF-1 increases cellular Beta-Catenin levels.
Insulin and IGF-1 stimulate the β-catenin pathway through two signalling cascades involving GSK-3β inhibition and Ras activation
https://www.nature.com/articles/1204064
"IGF-1 increased the cytoplasmic levels of β-catenin."
IGF-1 is produced in our bodies, in part in blood platelets.
There is not any blood in our inner ear fluid. Inner ear fluid is different from blood.
https://en.wikipedia.org/wiki/Endolymph
You can create a platelet rich composition of blood by putting drawn blood in a centrifuge which separates the platelets into something called platelet rich plasma, PRP.
PRP contains growth factors, including IGF-1.
The growth factors and other cytokines present in PRP include:
- 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
In your middle ear there is a semi-permeable membrane called the round window.
https://en.wikipedia.org/wiki/Round_window
So that's how you can deliver medicine to the cochlea, by filling up the middle ear, via eardrum injection, with a viscous solution containing X substance, it rests in the middle ear and the substance, if molecularly small enough, will diffuse through the round window membrane. That's why the various presentations produced by FrequencyTX, as well as their homepage emphasize that their products are "small molecule drugs", because this is exactly how FX-322 is delivered to the cochlea.
Other neurotrophic compounds are also being investigated to repair lost cochlear synapses by diffusion through the round window membrane.
Round-window delivery of neurotrophin 3 regenerates cochlear synapses after acoustic overexposure
https://www.researchgate.net/public...cochlear_synapses_after_acoustic_overexposure
So that's my theory, that IGF-1 works just like FX-322 to disable the Beta-Catenin destruction complex and cause the stem cells to proliferate into functioning hair cells except that IGF-1 is already produced in our bodies and needs to be manually introduced into the cochlea. Also PRP may be much safer than FX-322 because it is good for healing holes to the eardrum that would be caused by the injection.
Topical use of autologous platelet rich plasma in myringoplasty.
https://www.ncbi.nlm.nih.gov/pubmed/25794691
"Topical autologous PRP application during myringoplasty is safe and highly efficient and successful with no reported complication"
https://www.ncbi.nlm.nih.gov/pubmed/25794691
Now watch the nay-sayers purposefully push this post up the page with extremely long-winded ad-hominem attacks on me and Minbo Shim.
