Important questions about cell based treatments!

[Artista]

First thing that came to mind when reading the comments....
"The Pessimist is half-licked before he starts, The Optimist has won half the battle.." - Thomas A. Buckner"

[534623]

First thing that came to mind when reading the comments....
"The Pessimist is half-licked before he starts, The Optimist has won half the battle.." - Thomas A. Buckner"

...the most important half that applies to himself, when he begins his approach to a subject with the proper mental attitude. The optimist may not understand, or if he understands he may not agree with, prevailing ideas; but he believes, yes, knows, that in the long run and in due course there will prevail whatever is right and best."

Do you have a quote by Buckner, where he defines "in the long run" more specific?

[garethbale]

Do you have a quote by Buckner, where he defines "in the long run" more specific?

you're a strange little fellow...

[StinkySmurf]

What does your gut tell you on cell therapy?

Hey Breaking Bald,

Back in 2006, a German company called TeGeNeRo came up with a novel "Biological" treatment called TGN1412 which was meant to cure ALL autoimmune diseases!!! I'm talking, Diabetes, Eczema, MS, Crohn's, Ulcerative Colitis, etc etc...

So they started their Phase I clinical trial in 6 ppl in UK. But being a small company they didn't follow standard protocol and injected all 6 patients at the same time with different doses of TGN1412 rather than staggered dosing.

Long story short, within 1 hour of the injection, all 6 subjects developed a fatal condition called "Cytokine Storm", where they were banging their heads against the walls to try and kill themselves because they were in excruciating agony. Pretty much in most of them all their limbs solidified (turned into rock) and had to be amputated to save them!

Now, this happened very recently (2006) and the reason why it happened was because it was a "Biological". Now what biological refers to is a broad term that represent anything that is not a small molecule and is generally derived from animal or human tissues. This could be blood products, vaccines, proteins, or cell-based therapies.

Biologicals are VERY new in the field of medicine and a lot of regulatory authorities lacked expert scientists in these fields to carefully examine these products for potential harm.

Now, the TeGeNeRO incident changed EVERYTHING! The regulatory authorities realised the potential risks of biologicals and really amped up their regulatory requirements for these types of therapies.

I mean if you're involved in "regulatory affairs" you definitely know what a headache it is to get a biological agent approved!

So, even though there are potential risks associated, the FDA will be extremely stringent on Aderans to make sure every aspect of their trial proves safety to the best of their ability!

So, to make the story short, don't jump in to sign up for the trials but be patient. Once it is approved by the FDA, you can be pretty confident that it is a relatively safe therapy

Hope all this helps brother

Hey Desmond. Thanks for the really informative answers. I've been following this forum for a while, but I finally gave in and signed up because I couldn't stand not asking you these questions so thanks!

(1) I'm wondering if you can really compare TGN1412 to something like the Aderans or Replicel trials just because TGN1412 was a Phase 1 trial. TGN1412 had new problems that only showed up when they went from testing mice to testing people, but don't you think an Aderans or Replicel Phase 2 or Phase 3 trial is a bit safer because it's already been safety tested on people at that point? Isn't the risk of something like TGN1412 more for a Phase 1 trial like with Cell-Innovations that just started up in Australia?

Do you know of any good examples of toxic medicines like this where it didn't show up until phase 2 or phase 3 that it was suddenly deadly?

(2) What does your gut instinct tell you about the safety of Aderans and Replicel?

Logically speaking a new cell therapy presents the same risks as TGN1412 as you've shown already, but in terms of probability, how do you see the chances with Hair Multiplication?

Would you say that multiplying hair cells in a lab and injecting them back into your scalp is inherently an safer process than what TGN1412 was introducing into your system just because the hair cells are basically unmodified?

[Desmond84]

Hey Desmond. Thanks for the really informative answers. I've been following this forum for a while, but I finally gave in and signed up because I couldn't stand not asking you these questions so thanks!

(1) I'm wondering if you can really compare TGN1412 to something like the Aderans or Replicel trials just because TGN1412 was a Phase 1 trial. TGN1412 had new problems that only showed up when they went from testing mice to testing people, but don't you think an Aderans or Replicel Phase 2 or Phase 3 trial is a bit safer because it's already been safety tested on people at that point? Isn't the risk of something like TGN1412 more for a Phase 1 trial like with Cell-Innovations that just started up in Australia?

Do you know of any good examples of toxic medicines like this where it didn't show up until phase 2 or phase 3 that it was suddenly deadly?

(2) What does your gut instinct tell you about the safety of Aderans and Replicel?

Logically speaking a new cell therapy presents the same risks as TGN1412 as you've shown already, but in terms of probability, how do you see the chances with Hair Multiplication?

Would you say that multiplying hair cells in a lab and injecting them back into your scalp is inherently an safer process than what TGN1412 was introducing into your system just because the hair cells are basically unmodified?

You're welcome dude

In terms of risks you are right!

When it comes to clinical trials, Phase I is the riskiest of them all followed by Phase 2 and Phase 3 (hence the Tegenero tragedy)

If a drug has passed Phase 3, it is more than likely relatively safe so I wouldn't worry too much.

In my opinion, you can usually detect potential risks of a therapy based on the types of adverse effects reported during their trials. I'm talking about common adverse effects btw, there's always a very small minority that just don't tolerate a particular therapy. Based on these finding, you can extrapolate with high possibility what would be the worst possible scenario.

Here are some examples:

1) During Merck's Propecia trial, the main adverse event reported was impotence and ejaculation disorders, but all those subjects suffering managed to return to normal upon discontinuation of Propecia. So Merck assumed no risk would be involved! But we now know with hind sight, such adverse events may take a considerable amount of time to reverse in a small minority of people say 1 in 10 000.

2) Vioxx and Prexsig were anti-inflammatory drugs that were marketed for Arthritis. During the trials they simply detected slight changes in Liver function tests but no serious liver events were reported. Once they came on the market, fatal liver toxicity were reported all over the place which resulted in these drugs being taken off the market.

3) Now here's a hypothetical example: Let's say Histogen/Replicel/Aderans detected higher than normal levels of White Blood cell count post-injection, and the animal studies showed a potential for cancer (say at 1000 times the dose given to humans). Using this information, you could potentially worry that there may be a risk of cancer such as B cell lymphoma, etc.

Now, none of these cell-based companies have fully published their Phase 2 trials, once they do we will have a better picture of what to expect.

Moreover, I can promise you that me and a lot of ppl on this forum and in the medical field will be looking closely at every bit of info being released to evaluate the potential risks of these therapies. So make sure you stay tuned in the coming years

Hope that helps,

P.S. Replicel & Aderans are not exactly hair multiplication in the true sense of the word. They DON"T grow hairs in a lab and transplant it. They simply replicate specific cells that surround the hair follicle and provide the follicle with growth factors and nutrients. These therapies simply rejunevate existing follicles rather than making new ones. (This bit is from their latest update at Mesa btw. They announced: "They don't seem to be creating new follicles but rather rejuvenating existing ones"). Sad, but could be worse right

[Desmond84]

As for my gut feeling, I am a bit nervous about all 3 of them:

- Firsly, there haven't been a lot of autologous (your own) cell transplants done to date, so we don't really know if there is really a risk or not. Having said that, since they are simply your own cells, the risks would be quite low. The only things I would be worried about is the potential for cancer. Now we are lucky enough that Aderans has been stuck in Phase 2 for over 5 years, meaning by the time they release their product, some subjects would have been exposed to this treatment for well over 5-8 years. So, if there is a risk it should pop up in some of them (as sad that might be)

- Secondly, Histogen's using around 10 different growth factors. Some we know are safe, some are still to be investigated, so we'll just have to wait and see. Surprisingly, not a single adverse event has been reported in Histogen trials, apart from a case of eczema which is not a big deal

We just have to wait till we get our hands on their published data

[StinkySmurf]

Firsly, there haven't been a lot of autologous (your own) cell transplants done to date, so we don't really know if there is really a risk or not. Having said that, since they are simply your own cells, the risks would be quite low. The only things I would be worried about is the potential for cancer. Now we are lucky enough that Aderans has been stuck in Phase 2 for over 5 years, meaning by the time they release their product, some subjects would have been exposed to this treatment for well over 5-8 years. So, if there is a risk it should pop up in some of them (as sad that might be)

Yes, that is the silver lining to so many phase 2 trials for sure

[StinkySmurf]

P.S. Replicel & Aderans are not exactly hair multiplication in the true sense of the word. They DON"T grow hairs in a lab and transplant it. They simply replicate specific cells that surround the hair follicle and provide the follicle with growth factors and nutrients. These therapies simply rejunevate existing follicles rather than making new ones. (This bit is from their latest update at Mesa btw. They announced: "They don't seem to be creating new follicles but rather rejuvenating existing ones"). Sad, but could be worse right

Actually, I like follicular rejuvenation better than full neogenesis because if I'm only rejuvenating hairs, I don't need to worry about the cosmetic issues that come with a transplant, but if the rejuvenated hairs were only DHT resistant then we would basically have a cure because we would have a way to stop your baldness as soon as it starts.

I've seen you post several times that the new Aderans hairs might be DHT resistant, and I remember that being the rumor back when Intercytex was first planting hairs in mice and also when they did it in Japan recently, but I can't seem to find anything in the recent Aderans info that says the hairs will be DHT resistant.

Do you have any particular source or info that makes you think the hairs will be DHT resistant?

Thanks Demond!

[Desmond84]

Actually, I like follicular rejuvenation better than full neogenesis because if I'm only rejuvenating hairs, I don't need to worry about the cosmetic issues that come with a transplant, but if the rejuvenated hairs were only DHT resistant then we would basically have a cure because we would have a way to stop your baldness as soon as it starts.

I've seen you post several times that the new Aderans hairs might be DHT resistant, and I remember that being the rumor back when Intercytex was first planting hairs in mice and also when they did it in Japan recently, but I can't seem to find anything in the recent Aderans info that says the hairs will be DHT resistant.

Do you have any particular source or info that makes you think the hairs will be DHT resistant?

Thanks Demond!

Well, around 3 months ago I did a lot of research into what are Dermal papillae cells and dermal sheeth cup cells and why are we using them rather than the other 30 different cells around the hair follicles.

What I came up with was fascinating. here's some of those articles:

1) To date, we have only found Androgen receptors on the dermal papillae of hair follicles. Hence, the reason why Aderans most likely decided to use these cells! Here's the link:

http://www.nature.com/jid/journal/v98/n6s/abs/5612065a.html

2) Dermal papillae cells in balding areas express a much larger number of androgen receptors compared to non-balding areas. Here's a study if you wanna read further:

http://joe.endocrinology-journals.org/content/156/1/59.short

3) Here's the most AMAZING finding back in late 90's: "Dermal papillae extracted from occipital scalp hair follicles (donor area) lack Androgen receptors! Here's the link:

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2133.1995.tb08706.x/abstract

That's why I think at least in theory, DHT-resistance may be possible!

Cheers

[Desmond84]

2) Dermal papillae cells in balding areas express a much larger number of androgen receptors compared to non-balding areas. Here's a study if you wanna read further:

http://joe.endocrinology-journals.org/content/156/1/59.short

Btw, these guys compared dermal papillae from your pubic area, body hair, beard, balding areas and non-balding areas of the scalp.

They found that each region expresses different amount of receptors for Androgens. That's why both boys and girls both have pubic hair in their groin area because those dermal papillae express Androgen receptors. The beard dermal papillae only has androgen receptors in males, whereas the donor area of the scalp has no Androgen receptors!


It's a very fascinating read actually!

[Desmond84]

What I can't find out is:

1) How long do Dermal papillae last for before they have to be replaced with new ones?

2) How do Dermal papillae replicate? DO they replicate themselves or does a stem cell create more? If it's the latter, then we need regular injections of Aderans otherwise the stem cells would again produce DHT-sensitive Dermal papillae!

[StinkySmurf]

Btw, these guys compared dermal papillae from your pubic area, body hair, beard, balding areas and non-balding areas of the scalp.

They found that each region expresses different amount of receptors for Androgens. That's why both boys and girls both have pubic hair in their groin area because those dermal papillae express Androgen receptors. The beard dermal papillae only has androgen receptors in males, whereas the donor area of the scalp has no Androgen receptors!


It's a very fascinating read actually!

But since the implanted cells supposedly just wake up dormant follicles, I would think it doesn't matter that the donor area had androgen receptors because how do we know that property gets transferred to the dormant follicle when we wake it back up?

[Desmond84]

But since the implanted cells supposedly just wake up dormant follicles, I would think it doesn't matter that the donor area had androgen receptors because how do we know that property gets transferred to the dormant follicle when we wake it back up?

The health of the hair follicle is directly proportional to the size of dermal papillae. They've found that Dermal papillae in balding areas shrinks to the 1/3 of its original size. This reduces the amount of nutrients and growth factors that DP can provide the hair follicle thereby turning terminal hairs into vellus hairs.

Having brand new DP cells that have no androgen receptors would simply make sure follicles remain in their optimum health!

This is probably why Aderans could only revive follicles rather than regenerate new ones!

[StinkySmurf]

The health of the hair follicle is directly proportional to the size of dermal papillae. They've found that Dermal papillae in balding areas shrinks to the 1/3 of its original size. This reduces the amount of nutrients and growth factors that DP can provide the hair follicle thereby turning terminal hairs into vellus hairs.

Having brand new DP cells that have no androgen receptors would simply make sure follicles remain in their optimum health!

This is probably why Aderans could only revive follicles rather than regenerate new ones!

Ohhhhh!!!!!!! I see. A DP is not a follicle or some type of proto-follicle cell. A DP is something separate that feeds the follicle so the Aderan's solution is to supplement your diminished DP instead of trying to replace the reduced follicle?

Interesting... I would call that a cure if it can get into Phase 3 and it works as you say.

[HARIRI]

Guys, this is a great article about Stem cell transplant. Im sure its going to be very useful. Its been written well by Blake – aka Future_HT_Doc. There are many interesting findings from different top notch doctors about the technique in the end of the article.

Check it out

http://www.***************/hair-tran...gho-procedure/