Effective treatment for hair loss has advanced considerably over the past several decades, but for all that the multi-billion dollar industry has become, there still lacks a truly viable and permanent solution that addresses the needs of both men and women. For biotech company RepliCel Life Sciences, Inc. (REPCF), promising research around the regenerative properties of dermal sheath cup cells could prove to be the break-through that millions of hair-loss suffers have been waiting for.
For over a decade, leading hair biology scientists. Dr. Rolf Hoffmann and Dr. Kevin McElwee, have been studying the potential of dermal sheath cup cells to spark hair regeneration and the rejuvenation of miniaturized hair follicles. Hoffmann, RepliCel's Chief Medical Officer, discusses his research, the process of developing this treatment, and the critical steps the company is taking along the way to ensure that it is successful.
EQ: Can you start off by briefly talking about the history of your research and when you realized it had this kind of potential?
Hoffmann: Back in 1999, Dr. Kevin McElwee was the "postdoc" in my lab, and we found that the specific area on the very deep part of the hair follicle--what we call the "hair cup"--has the potential to regenerate hair in animals. So we studied this hypothesis on mice and it showed that the cells, when implanted, traveled to existing hair follicles and made them bigger. In addition, those cells alone, with no other mixture of cells, were able to induce the growth of hair follicles in the palms and soles of the mice, showing that these cells were able to generate hairs de novo [anew]. So we conducted our studies in 1999 - 2001 and published it in 2003. It's nice to have the animal data, but of course, we wanted to translate it to humans.
EQ: As you said, your initial tests with SCID mice proved to be very successful. Can you tell us how you think that could be translated over to humans?
Hoffmann: There's no small animal model for pattern baldness, but on the other hand, the mechanisms that lead to hair growth and hair loss are principally the same, meaning all hair cycling, hair follicle morphogenesis and so forth can be compared. That's why we don't study a specific disease. We do not study pattern baldness--we study hair growth. The results in the animal models showed that it's parallel to what you expect in humans because the principles of hair growth are nearly same. That's why we believe we can translate our findings to humans.
EQ: Obviously, pattern baldness is the leading disease for hair loss in humans, but your approach allows you to address other causes like chemotherapy or scarring as well, correct?
Hoffmann: Yes, and in all the instances where we see a hair follicle miniaturization--basically when the hair is getting thinner--it is usually because the cells in the hair root diminish in number and size. Usually, a higher number of cells in the hair root equals thicker hair. In chemotherapy, if the treatment is mild and only some cells die, the hairs do grow back but are miniaturized. Based on our research, the idea would be to get a biopsy of healthy hair follicles from the back of the patient's head before the chemotherapy treatment, grow the cells, and inject those cells into the patient after treatment. This could be a very promising clinical target because there's no treatment for chemotherapy-induced permanent hair loss.
Pattern hair loss is of course the most important target for us, and chemotherapy is number two. But there are also other more rare diseases, as well as other causes like scarring or alopecia that could be treated. Another important area is hair thinning that is due to getting older.
EQ: The key difference between RepliCel's research and others seems to revolve around the dermal sheath cup cells as opposed to papilla cells. Why are they such a key component to hair restoration?
Hoffmann: Our belief was that the real mesenchymal stem cells, or progenitor cells, are in the region of the cup at the base of the hair follicle. Once they are activated, they travel into the papilla and then stimulate hair growth. With every hair cycle, the complete papilla just disintegrates. Hair cycle means that the hair grows for many years, then every hair disintegrates and falls out, and a new hair grows from the same dermal papilla. In histology (the study of tissue), you don't see the dermal papilla. The cells are more dispersed and we believe that the quiescent papilla cells reside in these cup regions as a kind of niche and then they get activated in the papilla. That's why we think that these cells are less mature and hopefully more effective in treating permanent hair loss. Therefore, we don't use papilla cells.
EQ: Your pre-clinical results have shown evenly-distributed hair regeneration. How is this possible?
Hoffmann: Any kind of successful treatment must, of course, be cosmetically acceptable. This means no patchy spots; the hair must be evenly dispersed. What I think is fascinating in cell-based therapy is that the cells are already programmed. We do not reprogram them. They just do what they do in their normal life. They find the hair roots and don't go elsewhere. That's the reason why they found the miniaturized hair follicles and made them bigger in our animal experiments. These cells are not embryonic stem cells, they're much more differentiated. They're programmed in the sense that they allow and promote hair growth.
EQ: The company's first-in-man, Phase I/IIa clinical trial was started in December 2010, and the last patient was injected in August 2011. What's next for RepliCel in this trial, and what are you hoping to see in the results?
Hoffmann: Phase I trials are about safety, so a successful trial is, of course, about safety. Most people on the outside are not interested in safety; they're interested in hair growth. For the regulators, the first thing we must prove is that it's safe. A successful trial will prove that it's completely safe, with no adverse effects like ganuloma or tumor formations. A very successful trial would mean we see more hair growth at the levels we would expect to see in a patient treated with Rogaine®. So, a range of 10 percent to 15 percent more hairs per centimeter square is what we would define as very successful. If we see even more hairs than what is expected from finasteride (Propecia®) treatments, then we'd be very, very happy. So first of all, it's a safety treatment. But secondary, we are also looking for hair density and more parameters linked to efficacy.
EQ: RepliCel is conducting the clinical trial in Georgia, but the company is also working within safety parameters that meet FDA and European regulatory guidelines. Can you tell us more about that?
Hoffmann: This trial is currently being conducted in Georgia under Good Clinical Practice [GCP]. The protocol has been reviewed by the German authorities who helped form the basis of our current protocol with regards to the time of follow-up after injection and to the number of biopsies because the regulators were interested in seeing what happens underneath the skin. Therefore, this protocol is in line with all the requirements that the scientific advisor told us some years ago.
EQ: You mentioned Rogaine® and Propecia® earlier, and they've proven quite effective for the time being, but there's one market that they don't effectively address, and that's women. Your treatment could actually be very effective for hair loss in women, correct?
Hoffmann: Yes, that's true. I have been doing hair research and hair clinics for about two decades and there is no real treatment for pattern hair loss in women. The only drug available is Rogaine®, and it increases their hair density by about 12 percent at the most and they have to stay on Rogaine® for their entire lives. When you look to the statistics, it shows that very few women use it for many years. At most, maybe 90 percent use it for three to six months, and then move on to something else. This means that no women are really treated successfully. If you stop using the drug, all the hairs fall out after a very short period of time. In addition, the hair doesn't stay at this level either because Rogaine® does not interfere with the normal progress of pattern baldness, it's just a non-specific hair growth promoter. I've heard instances where people were going bald on Rogaine® because this product doesn't interfere with the normal course of the hair loss disease. Propecia® is different, it actually interacts with the etiopathogenesis [cause] of hair loss, but women are not able to take this drug -- it is for men only. Also, hair transplants are not a very good option for women who consider the surgery far too invasive. So, for women with miniaturization of the hair on the upper head, a cell-based treatment would be ideal. That's why I would think the biggest market would be women.
EQ: You and Dr. McElwee have been working together on this research for a long time now. Can you talk about the different roles and responsibilities each of you focus on?
Hoffmann: I'm driving the clinical development. As an example, it's really important to inject the cells in the correct depths. If it's too deep, then nothing happens. I developed an injector device with a manufacturer to ensure that the cells are always injected in the same way, at the same depth, in every patient. This was based on advice from the regulators who suggested that we make this process more robust in the day-to-day delivery of the treatment. I developed the protocols and I do the clinical work.
Dr. McElwee is more focused on improving the culturing process and developing an automated procedure for cell isolation. Kevin is more focused on the core science which is important for the clinical steps.
EQ: You could argue that hair loss in women has a much more drastic impact -- psychologically and emotionally than it has on men. Would you agree?
Hoffmann: Yes, much more. When judging the severity of a disease, you usually ask patients how they feel they will be impacted in their quality of life. When you ask women with hair loss about their quality of life, they will answer that they feel the same impairment as they'd feel with a diagnosis of breast cancer. It may sound absurd on the surface, but that's really how they feel. The reason for this is from childhood, women are confronted with advertisements, media and everything else stating that youth and beauty are related to a full head of hair. When they get older and lose their hair it is a big problem for many women and they often have very serious issues dealing with the loss.
EQ: If your research is successful, it could have a very significant impact on the medical industry, as well as on the quality of life for many people. That being said, on a personal note, what would it mean to you?
Hoffmann: This means a lot to me because I'm a very pragmatic person. I had more than 100 original articles published when I was in university. In contrast to many of my colleagues, I always said that science is good, but at the end of the day, science must help people. For me, this technology means a lot, because then we could say we were the first company that was able to really deliver an effective treatment for hair loss; especially to women. I run a hair clinic and usually 90 percent of the patients here are women, and they are so desperate for a treatment. All I can tell them right now is to use Rogaine®, but then it doesn't work. This technology could change lives tremendously for many, many women, so this would make me very proud.
Many people ask us if we see something on the clinical side? And I always say no, it's blinded of course. We must wait until the last patient comes in after six months, and then we'll know more and be able to speak in much more detail. But again, positive results would change my life and the lives of many others. I would feel very happy and very proud.