Q&A with Dr. Paul Kemp, Co-founder and CEO of HairClone

Dr. Kemp, Could this technique to culture dermal sheath cells solve the loss of inductivity problem?

http://www.nature.com/articles/srep26436

jarjarbinx Thankyou for this paper. There are lots of alternatives that we intend to test for. We plan to do this first by examining their influence on the ā€œtranscriptomeā€ of the cultured cells and then through in-vitro assays before studying their effect in a clinical setting.

Dr. Kemp:

Your website states the following:

I wonder if the precursor to this work should be to take small numbers of isolated original non-expanded cells and directly implant them into balding areas. This would provide an early understanding of the exact cell types and numbers needed to develop a working protocol. Itā€™s probably just my own ignorance of how things work, but it seems to me, most of the research Iā€™ve read starts off with an approach of starting with cell types that worked in mice, then highly expanding the human equivalent cells in culture, and then injecting them in humans in order to get regrowth comparable to minoxidil. Then the goal becomes obtaining the necessary funding to figure out how to maintain the inductivity of the cells in culture well enough to surpass the effects of minoxidil, in order to provide a commercially marketable procedure.

OK, so far, so good. But then we read a study from almost two decades ago that showed Dr. Jahoda implanted fresh DP cells in his wifeā€™s arm, and this resulted in zero hair growth.

From a patient perspective, weā€™re left with a feeling that, weā€™re another 20 years away from a marketable procedure, due to the fact that nobody has proven injecting hair follicle stem cells can ever reliably work in humans. IOW, weā€™re waiting to solve hypothesized fundamental problems before we ever do the research to show a) that this technique will work consistently in humans once the known fundamental problems are solved and b) what kind of cells we should have spent the effort to figure out how to reliably expand.

So letā€™s say, we spend 5 years and 25 million dollars figuring out how to expand the cells, and then we finally use them in human experiments and realize only one cell type even works. We focus on this cell type and realize we need to spend another 5 years and another 25 million dollars in order to figure out how to prepare the injection environment to favorably interact with the expanded cells in order to overcome the Jahoda problem shown 25 years earlier.

An alternate approach would be to inject non-expanded cells, and then figure out what kind of necessary co-factors are necessary to get the cells to reliably promote hair growth in humans. Hopefully, this research would be taking place in parallel with the research necessary to understand how to reliably expand the cells.

OK, so back to the cell bank idea. x% of donorsā€™ harvested cells would be used in the course of research, and the donor would be kept informed of how the cells were used along with the experimental outcomes of the cells. So if you used my cells in your research, I would know 90% had highly inductive traits at passage 1, x% at passages 2, 3, 4, etc. Thus, the money I paid to help fund the research begins to yield early fruit, and I feel as though Iā€™m a crucial part of the overall ongoing discovery.

Another level of donation would be the patient-pay protocol, where I pay to be tested upon, so you pluck my hair in the donor in order to extract stem cells from the anagen root, you also remove donor follicles in order to obtain non-cultured DS/DP etc cells. Then you pluck the targe recipient sites in mass(shown to result in a better hair regrowth environment), and you inject the cells into distinct recipient sites. OK, so I paid a lot of money, but I now know what kind of cells work in my head and the percentage of regrowth I can expect once the cell expansion problem is solved. And if I get subpar regrowth, then I can compare my results with other paying patients in order to assess where the research is at and what work remains to be done.

Letā€™s say I get great hair growth with the non-expanded cell type A but no other cells reliably work. Some time goes by, and itā€™s figured out how to better culture type A cells. At this point, I help fund another round that shows:

Uncultured cells = 90% response
Passage 1 = 85% repsonse
Passage 2 = 70% response
Passage 3 = 60% response
etc.

At this point, I can do the math on how many cells on average it takes to grow a follicle on my head compared to the number of donor cells I have available. My incentive to get on board with HairClone and provide money for research escalates with every experiment Iā€™m involved in.

@_JamesBond, some very good ideas there. But, a few points and questions:

Is there a practical and cheap way to measure cellsā€™ inductivity other than actually injecting them into the patientā€™s scalp and watching what happens? The techniques that were being used by Drs Christiano and Jahoda a few years back to determine % inductivity involved gene expression assays, which might be too expensive and complicated to use on a regular basis by clinicians or clinical researchers like HairClone, plus itā€™s an indirect measurement of which genes are switched on, from a pretty broad list of genes that are incidentally (or maybe circumstantially) linked to inductivity. Itā€™s not a direct measure of results. I could imagine this type of testing might make their treatment quite a bit more expensive for subjects or patients. Isnā€™t it just cheaper, and just as reliable, to simply inject the cells and look at the results?

If I understand Dr. Kempā€™s intentions, the answer is yes. The problem with injecting patients and waiting to see what happens is, you have to run human trials, which brings on heavy regulation and cost. Perhaps the biggest issue is, once you start the trial, youā€™re locked into a specific injection formulation for the length of the trial. So years can pass, and really not much gets discovered.

Iā€™m not a scientist, so I donā€™t know these things for certain, but I expect transcription assays can be developed relatively cheaply these days that allow you to quickly check the cells for specific changes that you have identified as inductive traits. This way, you ensure the cells are viable prior to partaking in costly and time-consuming human trials. Of course, part of the discovery is to better identify which changes are related to lost embryonic properties.

But then, why am I recommending human trials up front? My point is, it could make sense to have some small-scale trials up front that prove the procedure works with non-expanded cells that retain their original inductive properties. This way, you already have a treatment protocol established up front, and everyone involved knows it works, and it works well. This way, the effort put into expansion can be isolated to a specific cell-set that has been shown to work. Then, all you have to do is figure out how to expand the cells in a signaling environment that retains their original properties.

This is akin to working a problem from front to back as opposed to all the studies Iā€™ve read, which take a back to front approach of guessing which cell type might work best, taking years to figure out how to kind of expand it, and then inject it into human scalps in order to simply prove hair multiplication can work as good as minoxidil, but not much else is known. IMO, the front to back approach, in this case, speeds up and lessens the overall cost of discovery.

The way forward is to use ā€œAgileā€ development practices instead of partaking in big expensive waterfall projects that often result in failure. In waterfall, you do all the discovery up front, then design the entire project, including timelines, cost, requirements, etc. By the time waterfall experiments get implemented, the requirements and design are out-of-date, and youā€™re hopelessly locked into moving forward exclusively using this old knowledge.

So how is agile different? It is a process of ongoing discovery coupled with continual product releases. You identify which aspects of the overall final product have high value up front and develop them first (cheaply and quickly). From this, you learn enough to develop the next most valued aspect. And so-on-and-so-forth. So an agile hair multiplication project might go something like this:

Team 1 Iteration 1: Test the top currently suspected most suitable cell types in human scalps. Record % results.
Team 2 Iteration 1: Setup transcription assay infrastructure and increase knowledge of the subject.

Team 1 Iteration 2: Based on the findings of team1 iteration 1, select the cells that led to the most hair growth and passage them one time and inject human heads. Record % results.
Team 2 Iteration 2: Study changes in the cells that occurred in passage 1 cells.

Team 1 Iteration 3: repeat iteration 2 with passage 2 cells.
Team 2 Iteration 2: Study changes in the cells that occurred in passage 2 cells.

and so onā€¦

Of course, you donā€™t really need multiple studies to accomplish the above, you can study 10 passages of cells in a single experiment and discover the properties of cells that grow good hair compared to those that donā€™t. Now your one human study in, and you have a) proved whether or not non-passaged cells can cure baldness, b) the exact cell type that needs to be expanded in culture in able to produce a cure, and c) the transcription profile of cells that grow good hair compared to those that donā€™t. This would represent iteration 1 of an extremely fast moving and cost effective project.

Iteration 2 would be to run transcription assays in parallel in order to rapidly and cheaply figure out how to expand cells (identified in step 1) in culture that do no lose their inductive properties. Once this is accomplished, iteration three is to begin another human experiment , which is comprised of injecting expanded cells that have retained their inductive properties.

So now youā€™re two relatively cheap human experiments in, and you already have a cure. Of course, this is way easier said than done, but it provides a rough outline of the process.

I apologize to Dr. Kemp if Iā€™m off-topic and simply speaking nonsense.

@_JamesBond that is an excellent, very well thought-out approach, IMO. (You should work for HairClone!)

One thing Iā€™m still a bit unclear about: it seems that Dr Kemp is saying that HairClone can still conduct certain clinical operations based on its research ā€“ in other words, treat actual patients using protocols they develop incorporating new technology ā€“ without having to apply to do clinical trials, by taking advantage of a certain provision specific to UK law. I think we need to get a clear answer on this. To what extent will they be able to implement the products of their research immediately on patients?

I agree.

Those are very interesting posts from Roger_that and James Bond and the approach described is very similar to the one that we are already using as those who follow HairClone on Twitter or Facebook would have seen. As JB points out, there is a lot that could be learned from first using non-expanded cells and there are things that can be done while keeping within the Regulatory systems. It comes down to what the regulators define as a ā€œmedicinal productā€. Transplants are obviously composed of living cells and are not regarded as medicinal products (which is why hair transplants donā€™t need a ā€œMarketing licenseā€). The various National Regulators differ between where exactly the line between transplant and medicinal product lies and depending how a hair follicle is manipulated and how the cells are isolated then non-expanded cells can be used without being considered a medicinal product. Even when that line is crossed and the cells become medicinal products then in the UK there are several exceptions to the need for a marketing license that clinicians can use to provide a treatment to patients. These main provisions that are relevant to us are termed by the UK Regulators (MHRA) ā€œHospital exemptionsā€ and ā€œSpecialsā€ and there is a lot of information online about both of these, but to answer RT specific question, I have pasted a section directly from the MHRA documentation.


"Unless exempt, a medicinal product must be the subject of a marketing authorisation or product licence before being placed on the market. Regulation 167 of the Human Medicines Regulations 2012 (see Appendix 1) provides an exemption from the need for a marketing authorisation for a medicinal product which is supplied:

  1. ļ‚· in response to an unsolicited order;
    2)ļ‚· manufactured and assembled in accordance with the specification of a person who is a doctor, dentist, nurse independent prescriber, pharmacist independent prescriber or supplementary prescriber;
    3)ļ‚· for use by a patient for whose treatment that person is directly responsible in order to fulfil the special needs of that patient; and meets the conditions specified in regulation 167(2)-(8)."

So a Company cannot ā€œMarketā€ a product by advertising it or making claims about its efficacy but a clinician could use a product if they meet the conditions specified above and they feel that the treatment would benefit their patient.

As both of you have clearly grasped this can all be combined to develop an ā€œagileā€ pipeline of improving treatments and as these treatments develop we will gain more understanding about what works best for specific types of hairloss and what testing is needed to measure the important aspects of the cellā€™s transcriptome. And when all these are well understood and optimised, then we would have confidence to carry out the expensive and time consuming clinical trails needed to obtain ā€œMarketing Licensesā€.

And as part of all this, we want to develop this partnership of interested and educated patients and clinicians so that we can fund these steps and also create a ā€œcommunityā€ of people who understand our aims and are eager to take part in the process

I hope this helps and please feel free to continue the dialogue, they really help us

The transciptomics methods used in the Higgins et al paper are now provided as routine services by most major universities and although they arenā€™t cheap at the moment, they work but as you suggest they are a shotgun approach and measure everything many genes of which may be irrelevant but with more data we will get clarity about what measurements are critical and can therefore be better able to predict a cellā€™s inductivity before implantation

@PKemp Dr Kemp, I really appreciate the details and perspective youā€™ve provided here. As for UK law, I think those provisions in the MHRA give British clinicians a fairly wide latitude as to what can be done with patientsā€™ own cells ā€“ as you said, as long as there is no marketing of specific procedures.

Dr. Kemp, I understand your reluctance to use iPS cells if itā€™s risky so I donā€™t understand why Dr. Terskikh is progressing with his iPS cellular technology for hair loss at Sanford Burnham. Is there any chance that you might be being overly cautious?

Hereā€™s a story about Dr. Terskikhā€™s work with iPS cells to treat hair loss, heā€™s advancing his technology, and heā€™s also seeking funds to proceed. This is the ONLY technology that is presently capable of producing mass quantities of induced hair cells.

If I was HairClone I would talk with Dr. Terskikh just to stay in the loop if for no other reason.

jarjarbinx Thanks, we will definitely keep a watch on Dr. Terskikhā€™s work. As he says in his interview he is looking to raise the $1-5M funds to take his work to the next stage.

Sometimes some product gets a bad reputation and then it just canā€™t shake that bad reputation even if the productā€™s owners take remedial action and fix the product. I think that may be the case with iPS cells. I think that for some time there was a real and serious risk for cancer but I think scientists worked to solve that problem. I think the problem is either solved or itā€™s almost solved. See this recent article:

1 Like

And here are a few more articles about iPS cells and cancer.

https://www.regmednet.com/users/1034-alexandra-thompson/posts/5957-genetic-study-finds-induced-pluripotent-stem-cell-reprogramming-unlikely-to-cause-cancer

@_JamesBond your idea of an agile or ā€œfront to backā€ research method would also seem ideally suited to Dr Terskikhā€™s research with iPSCs.

Applying your methodology to the research plan outlined by Dr Terskikh, he could take dissociated, non-expanded DP cells (passage 0) and combine them with keratinocytes, assemble them in the biodegradable scaffolds he described, and implant those into human tissue. If the cells coalesce and assemble themselves into a follicle, it would be proof of concept.

Your idea makes a lot of sense, as opposed to first figuring out how to mass produce inductive DP cells from iPSCs. That is the challenging and expensive part that will take millions of dollars to develop. The scaffold implantation part is the easy part, but unless Iā€™m mistaken, it still needs to be shown to be feasible. At this point, I donā€™t think itā€™s been firmly established that the necessary component cells will spontaneously aggregate into a working follicle with all the complex parts of a working follicle, including the bulge and other parts involved in hair generation and cycling.

If that part (which is really the ā€œlastā€ step in Dr Terskykhā€™s proposed method of de novo follicle generation), can be proven up front, it would probably be a feather in his cap which he can then take to potential investors.

Same, as you said, for Dr Kemp and HairClone.

I donā€™t understand. Surely @PKemp is aware of Tsujiā€™s work and his 2020 anticipation, right? I mean unless youā€™re planning on releasing a ā€˜cureā€™ before 2020 then whatā€™s the point? No one is closer to finding a cure than Tsujiā€™s team at Riken. Replicel, follica, Histogen, and all these other companies which have had too many delays will be put into bankruptcy instantly. So whatā€™s the point of HairClone? It hasnā€™t even started any clinical trials - itā€™s basically pre-research! This is just so frustrating.

And donā€™t forget Follica. For all we know Follica will provide dramatic improvement and it could be marketed in 2018. And what about Kerastem? And then thereā€™s the issue that thereā€™s a ton of research into inductivity and someone might reveal a solution to the inductivity problem at the next HLC, which is just 8 months away. I think Replicel will probably fail (inductivity) but I also think new ideas about inductivity will probably be publicized this year or the first half of next year at the latest. So Replicel could incorporate that stuff into their technology and run it through one trial and release a breakthrough treatment in Asia. Shiseido may have already added some tech to protect inductivity in their version of the Replicel treatment and if they have then that could hit the market in 2018. And there are other treatments in clinical trials.

It seems to me that if HairClone has a nitch to fill for hair loss sufferers it would be to do something bold like getting together with Dr Terskykhā€™s and trying to use the iPS tech, or use some other tech that preserves hair inductivity during culture, and then offer said treatment to people early via a rapid access program.

The iPS cell trial that was halted (macular degeneration) have been re-started.

Some people here appear to be confident weā€™ll have a cure sometime between 2018 and 2020. This confidence seems to stem from a few statements by companies researching the cure who have provided zero details of how they expect to accomplish their ambitious goals. Iā€™ve seen these same promises continually for the last 20 years. Nothing has changed.

Look, all these companies are running into the same fundamental problems Dr. Gho ran into two decades ago and couldnā€™t figure out how to solve. Back in those days, I was in close touch with Dr. Moon-Kyu Kim who was studying genetic changes in cultured DP cells that caused them to loose their hair inductive qualities. About the same time, Jahoda placed non-cultured DP cells into a human patient, which resulted in zero hair growth. The only consistent growth he managed to get was when implanting stem cells with attached stromal tissue. Here we are 18 years later, and nobody has managed to further this early research and prove a cell-only treatment will consistently work in humans.

Aderans soaked huge amounts of money into researching a treatment and failed due to working the problem first in mice and then attempting to translate the mouse protocol to humans. Aderans = old-shool rule following = failure. OK, they didnā€™t completely fail. Their $100+ million investment resulted in mice growing massive amounts of hair. Unfortunately, their human patients are still bald.

Make no mistake, a lot of work remains to be done in this industry in order to bring forth a consistent cell-based treatment for hair loss. Dr. Kemp has a fresh approach that draws from the lessons of the software development industry. His ideas should be embraced.

Follica is just a more organized, professional version of dermarolling which has been tested for years on the forums. Such a disappointment that decades of research by Cots only yields a wounding process. The device may be more high tech then a simple polling thing with spikes but the results I bet will be similar.

Is there any proof that Shiesido is not using the same procedures as Replicel? Our best bet is Tsuji. Heā€™s the closest to bringing us a cure, Why is he not talked about more on here?

By the way @PKemp hereā€™s a recent interview with Alexey: Interview with Dr. Alexey Terskikh | Hair Loss Cure 2020