Peptides for arthritis?

[Deleted member 43589]

Thanks @testiculus! This does give some hope.

 

[testiculus]

A little more info on sprifermin. It is also known as FGF18. From a US lab supplier it is $3240/mg. So costs are not unreasonable for 100 ug dose every 6 months per joint. I don't know if it is available from any of the Chinese suppliers, but if so, they certainly would be cheaper. It is produced with genetically engineered e.coli, so anyone that has the capability to produce hgh would have the requisite skills and facilities neccessary to produce it.

 

[Deleted member 43589]

Thanks @testiculus. I am checking with my Chinese guy and see if he can find it.

 

[Cataceous]

Thanks @testiculus. I am checking with my Chinese guy and see if he can find it.

Bumping this to see if anyone has learned anything. I approached my healthcare provider about using this substance and not surprisingly was shot down immediately. Does anyone know if the above-mentioned source is very discriminating about its buyers? Any thoughts on the risks involved in getting some and doing a joint injection?

 

[mcs]

AOD 9604 + HA – VitaHealth Wellness

vitahealthwellness.com

 

[Deleted member 43589]

Bumping this to see if anyone has learned anything. I approached my healthcare provider about using this substance and not surprisingly was shot down immediately. Does anyone know if the above-mentioned source is very discriminating about its buyers? Any thoughts on the risks involved in getting some and doing a joint injection?

I totally forgot about this @Cataceous. I just sent a message to my friend in China to see if this fibroblast growth factor 18 (FGF18) is being produced and how much it cost if it is available. I should know in the next 24 hours and will post the reply.

 

[testiculus]

Bumping this to see if anyone has learned anything. I approached my healthcare provider about using this substance and not surprisingly was shot down immediately. Does anyone know if the above-mentioned source is very discriminating about its buyers? Any thoughts on the risks involved in getting some and doing a joint injection?

Not surprised that your doc isn't supportive as it's not FDA approved. For the US source, I've never bought from them, but they probably won't sell to an individual as their market is academia and biotech labs. You would probably need to setup an LLC and a mailbox at a UPS store or similar.

Given that a Phase 2 trial with 5 year follow up has been done without any significant adverse events, I would guess that the risk is fairly low. This is something where there's pretty good data on safety and efficacy. It's sad that it will probably never be brought to market as the FDA has put such ridiculous requirements out for approval that it would take a $1-2 Billion phase 3 trial to have a shot at approval. My guess is they are trying to protect the joint replacement market.

 

[Cataceous]

.. For the US source, I've never bought from them, but they probably won't sell to an individual as their market is academia and biotech labs. You would probably need to setup an LLC and a mailbox at a UPS store or similar.
...

Yes, the roadblocks are significant. Although you can place the order and even have a credit card charged, there is a further application process. Having a legitimate company with a PO box is insufficient. They want a business address for your "life science research facility". It may have been possible to come up with a plausible address in time, but that delay would further decrease the likelihood of acceptance.

 

[Deleted member 43589]

I totally forgot about this @Cataceous. I just sent a message to my friend in China to see if this fibroblast growth factor 18 (FGF18) is being produced and how much it cost if it is available. I should know in the next 24 hours and will post the reply.

@Cataceous, if forgot to mention, my friend in China said the following:

I am really sorry that we do not have this protein currently. I checked, if developing this product, it costs very huge.

Do not know how large its marketing is.

So the Chinese do not see any future market value of producing this protein. I am guessing it will eventually have the same issue here and have problem going through clinical trials to get FDA approval. Surgery/rehab brings in so much more money

 

[testiculus]

I'm not surprised that the Chinese aren't making it, given that it isn't a simple peptide. It's unlikely that it will ever be approved by the FDA. No one wants to put a $1B up for the trial they want, for what will ultimately be a political decision for approval. There's enough data to know that it works and is safe. The FDA is just all about protecting existing businesses.

The best hope would be for a compounding pharmacy to take interest in offering it and start marketing it to physicians for IA injections. Eventually the FDA would try and shut down the compounding, but hopefully there would be enough of user base by then to put political pressure on the FDA.

Such is the sad state of our medical system.

 

[Deleted member 43589]

I totally agree with you 100%. Much more profitable to just do surgery.

 

[Cataceous]

Another nice find by @ajax31. GDF11 is attracting interest in the anti-aging community. Now it looks like it's a possible treatment for arthritis. Like FGF18, this is a protein rather than a peptide. Because of the anti-aging market, GDF11 is more accessible than FGF18.

GDF11 protects against mitochondrial-dysfunction-dependent NLRP3 inflammasome activation to attenuate osteoarthritis​

Pengfei Zhang 1, Haoxin Zhai 1, Shuai Zhang 2, Xiaojie Ma 3, Ao Gong 4, Zhaoning Xu 5, Wei Zhao 6, Hui Song 6, Shufeng Li 7, Tengfei Zheng 8, Zhendong Ying 9, Lei Cheng 10, Yunpeng Zhao 11, Lei Zhang 12​

​

Abstract​

Introduction: Osteoarthritis (OA) is a highly prevalent degenerative disease worldwide, and tumor necrosis factor (TNF-α) is closely associated with its development. Growth differentiation factor 11 (GDF11) has demonstrated anti-injury and anti-aging abilities in certain tissues; however, its regulatory role in OA remains unclear and requires further investigation.​

​

Objectives: To identify whether GDF11 can attenuate osteoarthritis. To exploring the the potential mechanism of GDF11 in alleviating osteoarthritis.​

​

Methods: In this study, we cultured and stimulated mouse primary chondrocytes with or without TNF-α, analyzing the resulting damage phenotype through microarray analysis. Additionally, we employed GDF11 conditional knockout mice OA model to examine the relationship between GDF11 and OA. To investigate the target of GDF11's function, we utilized NLRP3 knockout mice and its inhibitor to verify the potential involvement of the NLRP3 inflammasome.​

​

Results: Our in vitro experiments demonstrated that endogenous overexpression of GDF11 significantly inhibited TNF-α-induced cartilage matrix degradation and inflammatory expression in chondrocytes. Furthermore, loss of GDF11 led to NLRP3 inflammasome activation, inflammation, and metabolic dysfunction. In an in vivo surgically induced mouse model, intraarticular administration of recombinant human GDF11 alleviated OA pathogenesis, whereas GDF11 conditional knockout reversed this effect. Additionally, findings from the NLRP3-knockout DMM mouse model revealed that GDF11 exerted its protective effect by inhibiting NLRP3.​

​

Conclusion: These findings demonstrate the ability of GDF11 to suppress TNF-α-induced inflammation and cartilage degeneration by preventing mitochondrial dysfunction and inhibiting NLRP3 inflammasome activation, suggesting its potential as a promising therapeutic drug for osteoarthritis.​

GDF11 protects against mitochondrial-dysfunction-dependent NLRP3 inflammasome activation to attenuate osteoarthritis - PubMed

These findings demonstrate the ability of GDF11 to suppress TNF-α-induced inflammation and cartilage degeneration by preventing mitochondrial dysfunction and inhibiting NLRP3 inflammasome activation, suggesting its potential as a promising therapeutic drug for osteoarthritis.

pubmed.ncbi.nlm.nih.gov

 

[Cataceous]

I'm not surprised that the Chinese aren't making it, given that it isn't a simple peptide. It's unlikely that it will ever be approved by the FDA. No one wants to put a $1B up for the trial they want, for what will ultimately be a political decision for approval. There's enough data to know that it works and is safe. The FDA is just all about protecting existing businesses.

The best hope would be for a compounding pharmacy to take interest in offering it and start marketing it to physicians for IA injections. Eventually the FDA would try and shut down the compounding, but hopefully there would be enough of user base by then to put political pressure on the FDA.

Such is the sad state of our medical system.

Fortunately this assessment appears to be overly pessimistic.

Phase 3 of the Sprifermin trial is ongoing, and researchers envision public access to this treatment soon. [R]​

I can also report that I have overcome the hurdles and obtained FGF-18, basically using the techniques you mention above. The homemade sprifermin also includes sucrose (5%), poloxamer 188 (0.1%) and phosphate-buffered saline. That's the most I've ever paid for sugar, but I didn't want to take any chances with impurities. Each dose is 2 mL with 100 µg FGF-18.

When you dig into the clinical trials you find that the more successful protocol actually consisted of a series of three injections of 100 µg each, separated by one-week intervals, and repeated every six months for two years. This makes the cost higher than suggested above, over $1,000 for each set of three injections.

The injections themselves are nearly painless, at least with the help of 10 mg of subcutaneous lidocaine at the point of entry. The tricky part is in the preparation—getting a sterile end-product with minimal waste of the expensive material. One issue is that a 0.22 µm filter can trap up to a milliliter of fluid. To get the cost down you can order a larger quantity of FGF-18, but this means dividing into aliquots and freezing the extra. Then you have to worry about stability if you don't have an expensive -80 °C freezer. I'm making do with a $300 -40 °C freezer.

In any case, my first injection was over a month ago, basically a test to see if it was doable. Except for a small amount of lost product it went smoothly. It could easily be a coincidence, but after two to three weeks there was a substantial reduction in discomfort in the joint. More recently this improvement started to reverse. There was a long delay in getting the second order of FGF-18, which is why the second injection wasn't done until this past week. I haven't decided whether to now do a new complete series of three weekly injections, or instead to count the one last month and only do two now. In either case I will do the next series in four months instead of six.

To possibly aid in cartilage growth I switched from iparmorelin (300 µg) to ibutamoren (10 mg). As reported elsewhere, I've also phased out my use of enclomiphene, which should contribute to higher IGF-1. My last measurement of this was some years back and was on the low side. I have a requisition to recheck and make sure it has not overshot and gone too high for my comfort.

I will continue to provide updates on occasion. It's probably wise to temper expectations in my case. The progression to medial bone-on-bone contact means that I would not have even qualified for the sprifermin clinical trials. Nonetheless, I am hopeful that even limited cartilage growth in the joint results in reduced discomfort and avoidance of a joint replacement.

 

[seppuku]

Fortunately this assessment appears to be overly pessimistic.

Phase 3 of the Sprifermin trial is ongoing, and researchers envision public access to this treatment soon. [R]​

I can also report that I have overcome the hurdles and obtained FGF-18, basically using the techniques you mention above. The homemade sprifermin also includes sucrose (5%), poloxamer 188 (0.1%) and phosphate-buffered saline. That's the most I've ever paid for sugar, but I didn't want to take any chances with impurities. Each dose is 2 mL with 100 µg FGF-18.

When you dig into the clinical trials you find that the more successful protocol actually consisted of a series of three injections of 100 µg each, separated by one-week intervals, and repeated every six months for two years. This makes the cost higher than suggested above, over $1,000 for each set of three injections.

The injections themselves are nearly painless, at least with the help of 10 mg of subcutaneous lidocaine at the point of entry. The tricky part is in the preparation—getting a sterile end-product with minimal waste of the expensive material. One issue is that a 0.22 µm filter can trap up to a milliliter of fluid. To get the cost down you can order a larger quantity of FGF-18, but this means dividing into aliquots and freezing the extra. Then you have to worry about stability if you don't have an expensive -80 °C freezer. I'm making do with a $300 -40 °C freezer.

In any case, my first injection was over a month ago, basically a test to see if it was doable. Except for a small amount of lost product it went smoothly. It could easily be a coincidence, but after two to three weeks there was a substantial reduction in discomfort in the joint. More recently this improvement started to reverse. There was a long delay in getting the second order of FGF-18, which is why the second injection wasn't done until this past week. I haven't decided whether to now do a new complete series of three weekly injections, or instead to count the one last month and only do two now. In either case I will do the next series in four months instead of six.

To possibly aid in cartilage growth I switched from iparmorelin (300 µg) to ibutamoren (10 mg). As reported elsewhere, I've also phased out my use of enclomiphene, which should contribute to higher IGF-1. My last measurement of this was some years back and was on the low side. I have a requisition to recheck and make sure it has not overshot and gone too high for my comfort.

I will continue to provide updates on occasion. It's probably wise to temper expectations in my case. The progression to medial bone-on-bone contact means that I would not have even qualified for the sprifermin clinical trials. Nonetheless, I am hopeful that even limited cartilage growth in the joint results in reduced discomfort and avoidance of a joint replacement.

Hi @Cataceous - curious about you adding the ibutamoren. How are you taking this, fasted, or with/near a meal? Is there any concern about it affecting blood sugar or causing insulin resistance at that dosage? If so, are you taking anything (metformin, berberine etc) to control that?

 

[Cataceous]

Hi @Cataceous - curious about you adding the ibutamoren. How are you taking this, fasted, or with/near a meal? Is there any concern about it affecting blood sugar or causing insulin resistance at that dosage? If so, are you taking anything (metformin, berberine etc) to control that?

The ibutamoren is taken at bedtime, hours after the last meal. I've been using a continuous glucose monitor and there's no evidence of negative effects in this regard. Which is to say that it didn't make things worse. But my Hba1c was already running high in the reference range in spite of good fasting glucose and insulin. I'm using the CGM as a tool to help bring down average glucose. Interestingly, sometimes these GH secretagogues can actually lower glucose. Apparently it depends on how much GH activity you get relative to IGF-1 activity. The latter tends to lower glucose.

 

[seppuku]

The ibutamoren is taken at bedtime, hours after the last meal. I've been using a continuous glucose monitor and there's no evidence of negative effects in this regard. Which is to say that it didn't make things worse. But my Hba1c was already running high in the reference range in spite of good fasting glucose and insulin. I'm using the CGM as a tool to help bring down average glucose. Interestingly, sometimes these GH secretagogues can actually lower glucose. Apparently it depends on how much GH activity you get relative to IGF-1 activity. The latter tends to lower glucose.

Thanks for the reply @Cataceous. I was considering giving it a try (same, low dose of 10mg) as i reacted badly to ipamorelin and mod grf 1-29 when i tried it. Someone in another thread mentioned that ibutamoren (somehow) helped with their shoulder impingement, which i have. Plus, it's potential anti aging benefits interest me. I'd probably struggle with the increased hunger side effect though, i think i need to do a bit more research on it.

 

[seppuku]

Thanks for the reply @Cataceous. I was considering giving it a try (same, low dose of 10mg) as i reacted badly to ipamorelin and mod grf 1-29 when i tried it. Someone in another thread mentioned that ibutamoren (somehow) helped with their shoulder impingement, which i have. Plus, it's potential anti aging benefits interest me. I'd probably struggle with the increased hunger side effect though, i think i need to do a bit more research on it.

So, i tried my first dose of ibutamoren last night, 10mg, and was very much looking forward to the enhanced sleep i keep reading about. Ended up having the worst nights sleep in ages, totally 'tired but wired' type feeling. I gave up around 4:30am and got up. Not the sleep result i was expecting tbh! Just done a bit of googling on the subject, and it seems fairly common, at least to begin with. I might leave it a day then try again at half a cap (5mg), see if i can tolerate that, then try 10mg again after a week. Thank god for modafinil!!

 

[seppuku]

So, i tried my first dose of ibutamoren last night, 10mg, and was very much looking forward to the enhanced sleep i keep reading about. Ended up having the worst nights sleep in ages, totally 'tired but wired' type feeling. I gave up around 4:30am and got up. Not the sleep result i was expecting tbh! Just done a bit of googling on the subject, and it seems fairly common, at least to begin with. I might leave it a day then try again at half a cap (5mg), see if i can tolerate that, then try 10mg again after a week. Thank god for modafinil!!

Ibutamoren is definitely not for me - i tried 5mg yesterday, in the morning this time. Within a couple of hours, i felt 'off' mood wise. That evening, i struggled to eat my dinner and ended up throwing most of it in the bin. My sleep last night was even worse than the night i tried 10mg - literally felt like i'd been poisoned, extreme joint pain and nausea. I was vomiting down the toilet around 1am, then spent the rest of the night awake and in pain. I guess there's always a small chance that what i bought was fake. But that's the end of my ibutamoren experiments i think.