Follicle Thought recently had the opportunity to interview Howard Leonhardt of Leonhardt Ventures about his interesting new invention aimed at hair regeneration, HairCell. The Chief Medical Officer of Leonhardt Ventures, Dr. Leslie Miller, also provided some input for certain questions in the interview. Dr. Miller is also Director of the USF Heart Institute and has co-authored one of the leading textbooks on Stem Cell Therapy for Cardiac Regenerative Medicine.
The topics covered in this interview include Howard’s extensive background working with stem cells to regenerate organs over 20 years ago, the planned clinical trial pathway to bring HairCell to market, and an in-depth explanation of how this technology actually works in the human body.
FT: For starters, can you tell us about your background in regenerative medicine?
Howard: In 1985 we began work with Dr. Robert O. Becker, the author of the book Body Electric, to explore use of bioelectric stimulation for improvement of blood flow. In 1988 we completed our first muscle stem cell repair of a large animal heart with Dr. Race Kao and Dr. George Magovern which was published in 1989 in The Physiologist. That same year I developed the ProCell stem cell micro needle delivery catheter that was later patented. In 1991 working with Dr. Stuart Williams we began work cell sodding stent grafts for aortic aneurysm repair. Dr. Williams patented the first method of taking stem cells and endothelial progenitor cells (blood vessel forming) from a person’s own fat tissue. In 1995 we completed the first ever percutaneous repair of an aortic aneurysm without surgery in Melbourne, Australia based on a Taheri-Leonahrdt (TALENT) series of patents. In 1998 our colleague and co-founder Dr. Doris Taylor published in Nature Medicine a landmark paper on muscle stem cell repair of hearts.
In 1999 we patented a biological pacemaker and published in The New England Journal of Medicine our results with non-surgical repair of thoracic aortic aneurysm dissections working with Dr. Christoph Nienaber. In 2000 we introduced the first genetic test for determining heart attack risk on the U.S. market the Pla2 polymorphism test working with Dr. Pascal Goldschmidt. Also, in 2000 I began filing a series of patents for mixed compositions for organ regeneration. In 2001 we completed the historic first-in-man non-surgical repair of a human heart in The Netherlands working with Dr. Patrick Serruys, Dr. Warren Sherman, Dr. Pieter Smits and Dr. Doris Taylor. We went on to complete and publish pilot, Phase I, Phase II and Phase II/III studies for muscle stem cell repair of hearts. That same year I began filing a series of patents for bioelectric stimulation based organ regeneration working at first with Dr. Juan Chachques in Paris and later with Dr. Jorge Genovese of Argentina. In 2003 working with Cleveland Clinic, the University of Florida and Florida International University, and the University of Arizona we began testing genetic modification of stem cells to improve regeneration results, and the use of nutrient hydrogels. We discovered the strong improved benefits from SDF-1, eNOS, CX-43, VEGF and other proteins. There are dozens of published papers now documenting the stem cell homing and regeneration benefits of SDF-1.
In 2008 I moved out west to California and set up an independent facility, Leonhardt Ventures, to focus on developing organ regeneration therapies with the combination of bioelectric regeneration signaling and micro infusion pump delivery of a mixed multi-component stem cell based composition. This work is done in collaboration with over 35 researchers from around the world with leadership from our great experienced management team, board, and advisors. Since then we have developed more than 30 new inventions related to organ regeneration and have spread out to address many organs including; brain, eye, aorta, artery, skin, breasts, pancreas, liver, kidney, bladder and yes – hair. From our original year, 2000, in which we developed signals of SDF-1 (stem cell homing) and VEGF (blood vessel growth) we have added IGF-1, HGF, EGF, eNOS, Activin A+B, RANKL, Follistatin and Tropoelastin. We are on the track to file patents on about a dozen more signals over the course of this year. We are working on GDF-10 BMP this week and NADA. In 2013 our main bioelectric regeneration research collaborator, and co-author , along with myself, of many of our patents, Dr. Jorge Genovese, published ‘In Situ Electrical Stimulation Drives a Regenerative Shift’ in the journal CELL TRANSPLANT. In total we have raised and spent over $145 million in developing our full portfolio of organ regeneration inventions so far since our founding.
FT: What lead you into the field of hair growth?
Howard: The pivotal moment to decide to go forward with hair regeneration was when we discovered the bioelectric stimulation signal for IGF-1. We originally targeted this cytokine for cerebral stroke recovery. We then read that studies have shown it works for hair regeneration. When we added signaling for HGF hepatocyte growth factor, Activin A + B (especially B), Follistatin, eNOS nitric oxide synthase, EGF epidermal growth factor, and Tropoelastin our confidence to pursue hair regeneration grew even further. We believe scalp matrix as a component of our HC-15 composition is also very important.
FT: What research is the HairCell technology based on?
Howard: The HairCell technology is based on our experience since 1985 with bioelectric, stem cell, and growth factor based organ regeneration. Many of the 10 proteins we control expression of with our stimulator have been studied already on a stand alone basis. A number of the components of our 15 component HC-15 hair regeneration composition have also been studied on a stand alone basis. We, ourselves, have complete studies documenting the benefits of repeat delivery of stem cells for organ regeneration purposes. We have combined all this cumulated knowledge and experience into one comprehensive treatment. We plan to publish and present animal study results and the first pilot human study of the full combination therapy in 2017.
FT: How did you come up with the 15 component hair regeneration composition?
Howard: 31 years of experience working on organ regeneration led us to these components.
Dr. Miller: Each of these components have been shown in numerous models and publications to have a beneficial role in tissue regeneration, and several such as IGF and Follistatin to have particular benefit in hair growth. The concept is that each would be additive to overall benefit. Research in the past has focused on individual proteins, but clearly the repair process in the body takes advantage of an array of molecules and cues, and we are building on that awareness. There is no data to suggest that there would be any adverse effect of combining these naturally occurring proteins, such as inactivation or reduction of benefit, and thus we believe that we are ahead of the field, specifically in the area of hair regeneration.There are 4-5 approaches now being used as therapies to achieve hair growth, but none are a part of the body’s native repair mechanics or contain important proven molecular agents such as our combination. We believe that we have the greatest strategy to not just show a small statistical benefit, such as 10% hair growth, but 3-4 fold improvements.
FT: We’ve never seen a device quite like this before in the hair growth tech industry. What kind of a clinical trial process would HairCell follow in order to become available to consumers?
Howard: We plan to implement a three part clinical path. First, one shorter path for just the scalp surface non-invasive bioelectric stimulation combined with topical ointments of known and already approved components. The second path is the same but with the addition of our HC-15 fifteen component composition embedded into the topical ointment. The third clinical path is for our full micro infusion pump delivery of our HC-15 below the scalp deep into the tissue. For all these we plan to start with a small scale dose escalation Phase I clinical trial of about 30 patients at a single center. Then we will go to a Phase II multi-center trial with about 150 to 350 patients. After that we move to a pivotal Phase II double blinded, randomized, placebo controlled trial in about 1500 patients. Our team has brought a number of products through all these phases of clinical trials in the past and knows the pathway well. We hope to start the first OUS (Outside US) Phase I trial later this year and the first U.S. based Phase I study early in 2017. We have reached out to OUS sites in Spain, Canada, Mexico, Czech Republic, Italy, The Netherlands, Argentina, and China. We have completed clinical trials in all these locations in the past. In the USA we have entered clinical trial planning with two centers in California. We are preparing an Institutional Review Board filing to be made for single center dose escalation Phase I safety studies as soon as our pre-clinical safety studies are completed which is expected this fall.
Dr Miller: This device is one of the most advanced approaches to generating electrical stimulation of some of the body’s most important native repair proteins in a directed manner that can emphasize individual target proteins in a sequential manner. There are others working in the area of what has become known as electroceuticals or electric medicine, but no one to my knowledge has the sophistication of this device.
FT: What are some of the reasons you feel that HairCell is a safe technology to use?
Howard: Nearly all of the components of our bioelectric therapy – SDF-1, IGF-1, HGF, EGF, eNOS, VEGF, Follistatin and Tropoelastin and components of our mixed composition – adipose derived stem cells, endothelial progenitor cells, Micro RNAs, exosomes, HGH, nutrient hydrogel, and scalp matrix have safety results documented in stand alone individual component studies. We, ourselves, and our research team members have sponsored over a dozen pre-clinical studies and over 100 patient clinical trial cases with stem cells or bioelectric stimulation of SDF-1. We sponsored over $7 million in pre-clinical studies looking at the safety and efficacy of SDF-1 alone working with the Cleveland Clinic and the University of Florida and teams in the Netherlands. Based on this data our team led the effort that led to the first ever FDA authorization for a combination gene (SDF-1) and cell therapy clinical trial for organ regeneration (heart) in 2009, the REGEN trial. We also sponsored the first repeat delivery organ regeneration muscle stem cell large animal pre-clinical study in Spain that was published in 2010.
We are utilizing natural bioelectric signals at very low voltages that we understand to be the natural signals the brain uses to get DNA of cells to release specific proteins for specific regeneration purposes on demand.
When you scrape your knee or elbow your brain gets an injury signal and then sends back a bioelectric signal to get SDF-1 to start releasing at the injury site. This SDF-1 is a stem cell homing signal that seeps out and is picked up by stem cells in the patient’s bone marrow that then release from the bone marrow and migrate to the injury site. Once enough stem cells sufficient to grow back the lost knee or elbow skin tissue from the scrape have assembled at the injury site the brain gets a starvation signal and then reverses the polarity of the signal and drops the voltage further and moves from the recruitment and proliferation mode to the differentiation (building new tissue) mode. In this phase your knee or elbow skin tissue is regenerated. What we are doing with our technology is playing back those natural signals on demand. If we point our bioelectric signal to your knee your brain/body thinks your knee has been scraped. All of the signals and composition components we use are the natural regeneration components found in your body that handle repairs everyday. For these reasons we are confident our safety studies will come out well as well as our efficacy studies.
FT: I notice you have a full ensemble of regenerative medicine tech companies in development using bioelectric stimulation. Can you tell us a bit about what you find so attractive about this technology and some of the successes you have seen from using it?
Howard: We, I, have invested everything, ALL we earned from all our previous inventions into this combination organ regeneration technology because we fully believe in it.
Dr. Miller: Our approach is totally new. There are others that are working in electrical stimulation, but none have been in the field as long as Dr Leonhardt, and none have worked on developing a technology to have the ability to individually target specific proteins and the sequence of those stimuli. In addition, no one has developed the combination of very beneficial agents to bolster the benefit of the bioelectrical stimulation. In short, we believe that we have developed the most novel, comprehensive, and science-based strategy to treat not only hair growth, but many other common medical problems.
FT: Is there anything else you’d like to mention about the HairCell technology and your current progress moving forward?
Howard: We are bringing 31 years of un-paralleled research into this development. In the 1980’s we introduced the leading predictably compliant cardiovascular balloon catheters. In the 1990s we developed that which is today the leading non-surgical system for repairing aortic aneurysms and the first percutaneous heart valve. In 1999 we launched the first stem cell company for heart repair. Our treated patients improved 95.7 meters in exercise capacity testing over randomized placebo control patients. We are more confident about the combination of bioelectric regeneration signaling + micro infusion pump delivery of the fifteen component regeneration composition for organ regeneration, including hair, than we have ever been with any device or therapy we have developed before.
Dr. Miller: We have developed an approach that is both non-invasive and simple to deliver, and yet is perhaps the most advanced multi-component system ever tested in hair growth. It will be very well tolerated and show improvement in a relatively short period of time. Importantly, we have an escalating regimen that can employ the use of stem cells for those with the most difficult conditions. We will move quickly from the initial group of 30 patients to a much larger pivotal trial that will lead to FDA approval for commercialization. The study will start very soon and we are confident that it will enroll very quickly as hair loss is such an important problem for thousands of men and women.
FT: Thank you Howard and Dr. Miller for taking the time to speak to us.
Wow, things just got real, huh? I’m fascinated by the potential of using the body’s own natural electrical signaling to stimulate organ regeneration. I look forward to the results from HairCell’s animal studies and the human pilot study in 2017.
When Howard was responding to my questions for the interview he provided many citations to scientific documentation about his research in regenerative medicine, his patents, and articles on the components of the HairCell composition. I decided that it would work best to have all of that information listed separately so I’ve listed many of the citations here for your perusing interests.
Howard J Leonhardt’s Patents
Article on Google’s parent company investing in bioelectric medicine
Scientific article on stem cell homing factor (SDF-1)
Scientific article on bioelectric stimulation and regeneration
Scientific article on IGF-1 and hair growth
One of Howard’s earliest stem cell delivery patents
A pivotal study for SDF-1 and nutrient hydrogel that was sponsored by Howard
The REGEN trial of 2009 – First approved gene-modified stem cell therapy trial