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Replicel regenerating existing, miniaturized follicles, David Hall CEO interview


#1

Thanks to Ahab for telling us about this interview on Spencer’s show. First of all, the interview was very good, and appreciation to Spencer and Mr. Hall for doing it. David Hall very clearly explained where Replicel stands to this point, answered a lot of questions that might occur to us (but not all the questions I could think of), and Replicel also should be complimented on its transparency. Mr. Hall candidly admitted some failures and challenges at Replicel, too, which convinces me that this company is not getting over-enthusiastic or bragging about technologies that are not feasible or have little chance of being worked out (like some other companies we know… Can anyone say Foll-- OK, I won’t – but you get my point~)

Anyway, here’s my very brief analysis. Clearly what Replicel is doing, according to Mr. Hall, is reviving or regenerating existing, miniaturized follicles, RATHER than generating new follicles.

This is significant for a few reasons. One is, Mr. Hall stated that the success of Replicel’s procedure will most likely be tied to “hitting” the miniaturized follicles with injected cells while they are in the proper hair growth phase. That is, he indicated that the injections are likely to be successful if the cells can reach follicles which are in growth (anagen) phase, but wouldn’t be successful if the follicles they hit are in dormant (e.g., telogen or catagen phases).

Well, the first thing I can infer from that is, obviously, that they’re regenerating existing follicles rather than creating new ones (which I’ve already stated above).

The second thing I infer from that is that success (or yield of regenerated follicles per injection) will be dependent on the ratio of follicles in anagen phase to those not in anagen phase, on a particular patient’s scalp.

The third thing I infer is that since most balding men have far higher numbers of follicles in sleeping (e.g. telogen) phase than in growth (anagen phase), then yield per injection will likely be lower than we expect or hope, for a given person.

The reason for that is that in AGA, what happens is that the disease process lengthens the dormant phase, and shortens the growth phase, of affected follicles. The ultimate end of this process is that growth phases become exceedingly short (maybe days?) and telogen (resting or sleeping phase) becomes extremely long.

The fourth thing I can infer is that multiple sessions or multiple injections of Replicel’s cells could gradually increase yield. (Something to this effect was said by Mr. Hall).

The fifth thing I can infer is that possibly for some people whose growth phases have become ridiculously short, the procedure may help them only a minimal amount, if at all.

The sixth thing I want to note is that you can’t discern with 100% accuracy what the growing-to-sleeping ratio of follicles is, even in a substantially bald man. However, you can get an idea. If there are still significant numbers of hairs on the scalp sprouting out, but nonetheless the hair is still very thin and the scalp is largely denuded, then that person still might have a relatively high proportion of hairs in growth phase.

On a normal (non-balding) scalp, the ratio, I believe, is about 3:1 (growing to sleeping).

On a very bald person’s scalp, in the balding areas, maybe the ratio is 1:5 or 1:10 or something like that.

Then, according to Mr. Hall, only 1/10th of the injected cells (or less) might be fortunate enough to “hit” a follicle in growth phase, which just tells you about the inherent challenge of this kind of procedure.

The final thing I wanted to mention is that treatments like Sanford-Burnhams’s are NOT dependent on the state of the follicles in your scalp. They are wholly independent of that, in fact, because they create NEW FOLLICLES. Yes, they actually create brand new follicles.

As Mr. Hall said, Replicel’s procedure will be a good treatment, but not a cure.

By the same standard, then, maybe a treatment like Sanford-Burnham’s, which is based on completely different technology, is a real cure.


#2

What if you could get all of your follicles to go into anagen before injecting the replicel treatment???


#3

On the part of my head that I can get a really close look at–the area where my original hairline was and the start of my transplants, which are higher than my original hairline–I can see zillions of vellus hairs, all densely packed.

Since these are vellus hairs–i.e., tiny fibers sticking out of the follicles–wouldn’t that mean they are in the growing (aka, Anagen) phase?

I can also see a lot of vellus hairs in the bald spot at the back of my head when I use two mirrors and backlight the area.

I am on rogaine and Avodart, which may be why I still have vellus hairs so many decades in areas that haven’t had terminal hair in thirty and more years.

Maybe the first thing to do is to take a DHT blocker and maybe also Rogaine (I’m pretty sure rogaine works by prolonging the Anagen phase), before getting replicel.


#4

Did you also listen to the very recent (recorded less than a week ago) interview of the CEO of Histogen?


#5

[quote][postedby]Originally Posted by jarjarbinx[/postedby]
What if you could get all of your follicles to go into anagen before injecting the replicel treatment???[/quote]

Well, if we had something that could switch all the follicles in a bald scalp to anagen, that in itself would effectively be a cure for hair loss, or at least the best treatment we’ve had so far.

JAK inhibitors or PGD2 inhibitors might be able to do this, at least if they work as hypothesized (but not yet proved).


#6

I think yes, they could be growing phase, albeit a very weak one because the numbers of their DP cells have been greatly reduced.


#7

Rogaine might do it.

[quote][postedby]Originally Posted by jarjarbinx[/postedby]
What if you could get all of your follicles to go into anagen before injecting the replicel treatment???

[postedby]Originally Posted by roger_that[/postedby]

Well, if we had something that could switch all the follicles in a bald scalp to anagen, that in itself would effectively be a cure for hair loss, or at least the best treatment we’ve had so far.

JAK inhibitors or PGD2 inhibitors might be able to do this, at least if they work as hypothesized (but not yet proved).[/quote]


#8

Soon after I started taking Propecia in 1998, I saw the bald spot in the back of my head get smaller.

This happened by the growing of new hair around the periphery of the bald area, reducing the diameter of the bald area by almost an inch.

I’m pretty sure that this happened when vellus hairs were stimulated by Propecia to grow into terminal hairs.

The moral of the story being that where there are vellus hairs, there may be termainal hairs again.


#9

The histogen interview was great too! She answers all the questions and explains the delay. She also describes her product thoroughly. It’s great news about the growth factors because I thought it would wear off over time, but thing is all the’re needed for is to jump start the process of rejuvenation and acts as an antagonist to the effects of baldness. Mexico late 2017 potential availability


#10

In 2003, Mc Elwee showed that DSC cells have equal ability to create new follicles as DP cells. In addition, they have the ability to migrate into existing follicles and restore hair growth. Whether or not Replicel targets rejuvination of existing follicles or new follicles (or both) is purely a matter of their choice of delivery technique (Note that DSC and DP cell techniques have different effects in humans than in mice, so it’s not simply a matter of extrapolation of the following study).

http://www.nature.com/jid/journal/v121/n6/full/5602058a.html

Unfortunately, those who are interviewing Replicel seem to have lost touch with the existing science behind this technique, as recent interviews have provided little new information about the technique. We continue to rehash the same old BS without advancing what we’ve known for years. This mimics how scientists and companies do their research–thinking inside the box in order to retain status, safety, and a comfortable lifestyle.

Sanford-Burnham has zero ability to grow more hair based on cell type (DP vs DSC). In fact, much of the existing research shows that DP cells have limited induction ability when used in human beings. Despite DP cells apparent limitations in human research, what is important about the two techniques is the loss of cell inductivity in high-passaged cells. Sandford Burnham’s advantage is unlimited full-strength cells, which even if they don’t result in creating DHT-resistant follicles can be re-injected throughout the life of the patient (as long as DP cells are a good candidate for human injection).

Has anybody asked Replicel about the genetic changes their small sample of donor cells undergo when being multiplied in large numbers in culture? Or is this still a complete unknown at this late stage of the game?

In order to work, it seems Replicel merely needs to be used off-label with enough follow-up treatments to target all balding follicles. In the meantime, the existing hair that would otherwise undergo future fallout will be immunized to baldness, so it is effectively a cure. Perhaps the most useful aspect of this cure is, young people just beginning to bald can simply be immunized and never have to deal with this mess in the first place.

With Sanford-Burnham, a deep understanding of cellular microclimates is probably necessary in order to create DHT-resistant cells. It’s not that it isn’t possible; it just requires a much deeper understanding of culturing environments. As we can see through the example of Replicel (who use a purely off-the-shelf culturing solution) having a deep understanding of the culturing environment is well beyond the scope of a typical startup company and will add unnecessary years to the release of any envisioned product. That, and the varied nature of Sanford-Burnham’s research leads me to believe their treatment is WAY into the future. Their main goal is to generate headlines, which in turn generates additional research donations (similar model to Christiano and the rest of these unmotivated slow pokes).

Some might argue that if DSC cells were in unlimited supply, Replicel would be a cure (along with Sanford-Burnham). But there’s an interesting aspect lurking behind this argument.

Gho simply plucked hair from follicles, cultured the available stem cells, and then injected them in order to stimulate the existing shrunken follicles. His protocol could easily be adjusted to cure many, if not most or all people, because the available full-strength cells for injection are purely unlimited.

The problem is, researchers want to be able to inject a patient once or twice using a very small initial cell collection technique and then not do any future injections. This way, they can clear the regulatory agencies and get a simplistic prescription label for the product. This is contrary to what we know about the current crop of techniques, which is, in order to work consistently across a broad population of patients, they need to be re-administered a large number of times. Nobody wants to design a trial to account for that because it adds additional complexity, time, and expense. It also fails to target a broad range of patients with a single treatment protocol and instead calls for “individualized” treatment for each patient. This is a huge no-no when attempting to commercialize a treatment prescription. So when they only get an average growth rate of 10% in an already bald area (read poor visual results), and the response is wildly inconsistent across the treatment population, it’s not seen as commercially viable according to the prescription label they’re seeking, so they simply give up.

Very little has changed since I started following these treatments in the late 1990’s. We’ve known about a cure since then, but companies don’t find it to be commercially viable, so they won’t pursue it. If a super rich bald man (like Donald Trump) wants to pay for a full head of hair, I can give it to him, as can many people much more knowledgeable and capable than myself (as long as they’re willing to think outside the box, which I expect they are not). Startup companies cannot do this, because their hands are tied behind their backs trying to create a simple protocol that works on everybody via a few magic injections. So our options are absolutely limited, and the pace of progress is less than that of a snail. After 17 years of sitting on a cure, we are seemingly at the exact same point we started–hog tied and hoping for a lucky break that rewards an otherwise blind startup company.

I’m beginning to believe the way forward is to stop thinking about curing everybody and start thinking about curing only a few very rich people who want a full head of hair. Either that, or perhaps crowd fund a few lucky suckers to be the first to be cured and then hit the news with it. Once you cure two people, no matter what the cost, you will start an avalanche of research and funding to cheapen the procedure in order to deliver the treatment to the masses (I.E. funding would be the last thing you would have to worry about).

In my opinion, the cure for baldness is not waiting for some future discovery. It’s simply waiting on someone, who is well funded, to simply use the available science in a semi-creative manner. Unfortunately, much like the state of the world in 2003, when Mc Elwee released the above study, nobody is willing to do so. The supposed smartest members of our society mostly sit around and think inside the box until they die. In the meantime, a new generation of ideas is born that causes a small advancement, and then we wait for that generation of thinkers to finish thinking inside the box and die, so that we can get yet another generation of inside-the-box thinkers. In the meantime, we all die bald.

I’m convinced, a cure for baldness already exists, but either nobody can think clearly enough to perform it, or nobody is willing to pursue it due to life inside the safety of the box being far too comfortable. I expect that even I could cure baldness if I had moderate funding to lead a team of scientists in a small lean company in a lightly regulated country. To speed up the process, I would simply buy ARI’s existing knowledge base and continue forward from there. Curing baldness is not about figuring out point B. We already can conceive point B. It’s about, how do we get from point A to B when 100% of the world’s VC remains uninterested. Once we get to point B (completely cure two people using existing science in conjunction with outside the box techniques), we can more easily move to point C–curing the entire general population. Unfortunately, the regulatory agencies are not set up to support this model, and nobody is willing to buck the trend.


#11

I agree that JAK inhibitors or PGD2 inhibitors or minoxidil might do it and
I was also thinking the new Wnt mediator, SM04554, that is in clinical trials
might also do it. It looks like there might be lots of ways to possibly do it.

[quote]Rogaine might do it.

[postedby]Originally Posted by jarjarbinx[/postedby]
What if you could get all of your follicles to go into anagen before injecting the replicel treatment???

[postedby]Originally Posted by roger_that[/postedby]

Well, if we had something that could switch all the follicles in a bald scalp to anagen, that in itself would effectively be a cure for hair loss, or at least the best treatment we’ve had so far.

JAK inhibitors or PGD2 inhibitors might be able to do this, at least if they work as hypothesized (but not yet proved).

[postedby]Originally Posted by Ahab[/postedby][/quote]


#12

James, not sure what you mean here:

The two statements bolded above seem to be directly contradictory. If they have “zero ability to grow more hair”, then what do you mean that their “advantage is unlimited full-strength cells”?

Now that is a good question!


#13

[quote]The two statements bolded above seem to be directly contradictory. If they have “zero ability to grow more hair”, then what do you mean that their “advantage is unlimited full-strength cells”?
[postedby]Originally Posted by roger_that[/postedby][/quote]

Sorry, I didn’t mean DP cells do not have the ability to grow hair at all. I meant, pure DP cells do not possess the ability to grow more hair than DSC cells based on cell type alone. As seen in Mc Elwee’s study (and others), both types of cells can result in a similar amount of new hair growth, due to possessing similar embryonic properties (at least in mice).

The advantage of SB’s technique is they don’t have to worry about their cells losing embryonic properties when attempting to create enough of them to cure a NW 7. OTOH, the advantage of donor resident DSC cells (Replicel) is their innate ability to immunize all recipient follicles to the ravaging effects of DHT (and evidence exists they could be more inductive in humans than DP cells). The disadvantage of both techniques is the need for scientific status, validation, and funding leads to thinking inside the box. Thus, it takes about 20 years to perform a few good years of well-thought out research.

Take Shiseido for example. They exists in a highly favorable regulatory environment and have plenty of funding to bring this to market. But they are doing nothing more than throwing some DSC cells into an off-the-shelf stem cell culture growth media and reagent solution that was frozen in time a decade ago along with a target cell extraction technique from the same era. When you change one single aspect of the research, you go back 10 years and start all over at phase I. I suspect, given the regulatory environment in Japan, this would be quite easy to circumvent. But I also suspect nobody has any plans to do so do to so, given the fact that this would break their contractual obligations with Replicel.


#14

Ahab and RT:

That’s a great idea and certainly worth the effort. Unfortunately, Replicel cannot incorporate changes into their existing protocol. Otherwise, it resets the clock at the FD. The best we can hope for is they will be able to prove enough efficacy to release the product in Japan (I.E. the basic no-frills model first dreamed up 10 years ago). Then doctors would be free to use it in an off-label (read more intelligent) manner in order to produce better results.


#15

[postedby]Originally Posted by James Bond[/postedby]

Take Shiseido for example. They exists in a highly favorable regulatory environment and have plenty of funding to bring this to market. But they are doing nothing more than throwing some DSC cells into an off-the-shelf stem cell culture growth media and reagent solution that was frozen in time a decade ago along with a target cell extraction technique from the same era. When you change one single aspect of the research, you go back 10 years and start all over at phase I. I suspect, given the regulatory environment in Japan, this would be quite easy to circumvent. But I also suspect nobody has any plans to do so do to so, given the fact that this would break their contractual obligations with Replicel.[/quote]

Very good comment here. Unfortunately, without any substantial changes to their protocol, their efficacy is probably not going to cut it. If they have to go back to the drawing board (phase I), they are, for our purposes, essentially finished. The process is too long, too expensive. It wouldn’t be here before 2030 and even that is besides the point - which is they wont have the resources or even the interest in starting over due to huge financial costs and not being able to reap a profit in a realistic time frame.

I hope i’m wrong and phase II studies surprise us, but not holding my breath on that. My guess is that they’ll see similar results to phase I, maybe a few percentage point increases. But, nothing to wow us. They’d need to crush minox/fin results to get people to pay up for an expensive treatment.


#16

OK, understood. But so far, from Replicel, we haven’t seen any significant photographic results (or anything solid reported) from DSC cells, whereas from Sanford-Burnham, we’ve actually seen a dish full of terminal follicles grown from stem cells. So, even if you correct for the difference of cell types, to this point, Sanford-Burnham has shown us much more solid evidence.


#17

I agree that SB looks very promising. But to me, it seems like a typical experiment I’ve seen where exciting ground has been broken and then just filed away and sat on for years. I say this mostly, because the stage of research is currently “very early.” Thus, I see it as taking much time to unfold.

Despite Replicel being at a much more advanced stage of their research, I’m not high on them either. IMO, they’re not really doing much different than those who’ve already tried and failed. Don’t get me wrong. I believe they are sitting on a cure. Unfortunately, IMO, they are doing just that–sitting on it.


#18

I just listened to a very recently broadcast interview of Dr. Angela Christiano, about the successful use of JAK inhibitors in the treatment of Alopecia Areata.

There was some indication during her research of JAK inhibitors, that they might also be effective in treating mpb.

Since these inhibitors were topically applied versions of drugs already approved for oral use in the treatment of other diseases having nothing to do with hairloss, it might be reasonable to conclude that applied topically, they should be very safe.

And if I heard correctly, physicians are already prescribing off-label use of these inhibitors by writing Rx’s for these drugs being compounded into topical appilcations for their alopecia areata patients.

Think there might be any doctors willing to do this for mpb patients? To be extra careful, I’d consider applying the drug to just a small area of my scalp to see if it does anything. I suspect after hearing that interview, the drug will do a lot!