The Science of Hair Regrowth
Hair loss is a condition affecting men and women of all ages, and often comes with significant psychological and social impacts to those affected. Hair loss research is important not only for the general appearance and maintenance of hair, but also for a person’s psychological well-being. (1) Hair loss is caused by a number of factors, so treatments for hair loss also vary in their approach.
Current Treatments for Pattern Hair Loss
Androgenic alopecia, or pattern baldness, is the most common form of hair loss. It is caused by various factors, one of the most important being a buildup of dihydrotestosterone (DHT). DHT is a hormone converted from testosterone by an enzyme called 5α-reductase. DHT is classified as an androgen and is important for male sexual development, but also present in women. While the exact mechanism remains unclear, it is thought that increased blood levels of DHT leads to shorter hair growth cycles and thinning of hair over time.
Hair loss treatments approved for this condition include minoxidil, finasteride, LLLT, and dutasteride. Minoxidil, finasteride, and LLLT are FDA-approved treatments for androgenic alopecia. Dutasteride is currently only approved as a pattern hair loss treatment in Japan and South Korea.
Minoxidil (Rogaine®) acts as a vasodilator, expanding the blood vessels underneath the scalp and allowing more oxygen and nutrients to feed the hair follicles. Typically it is used as a foam or ointment and used topically on the affected areas of the scalp. Minoxidil is typically the first treatment option given to patients experiencing androgenic alopecia, and has been a staple in treating hair loss since 1988. (2)
Finasteride is a medication known as a 5α-reductase inhibitor, and it works by blocking DHT, the main culprit in AGA. Since 5α-reductase is the enzyme responsible for converting testosterone to DHT, blocking this conversion decreases levels of DHT in the body. As DHT levels decline, the hair growth cycle becomes more normal, and hair follicles can regain some of their thickness.
Dutasteride is another 5α-reductase inhibitor, but is only approved for the treatment of hair loss in certain countries such as South Korea and Japan. Like finasteride, dutasteride is typically used to treat men with an enlarged prostate, but is also commonly used off label for AGA. A 2019 scientific review that compared the effectiveness of both finasteride and dutasteride found that while both drugs showed similar rates of side effects, dutasteride seemed to show better efficacy. (3)
Low-Level-Laser Therapy (LLLT) uses short wavelengths of light (in the red light range on the electromagnetic spectrum). This type of light has been shown to stimulate the growth of hair, and has evolved into its own hair loss treatment, known as laser hair therapy. The exact way this happens is not known, but the most widely accepted theory is that LLLT stimulates stem cells responsible for hair growth, moving them from a “dormant” phase to an actively growing phase. This is in addition to the increased blood flow to the area that LLLT provides. This treatment option provides a drug-free alternative for those in which medications have been unsuccessful, or as an add-on treatment to existing hair growth regimens. (4)
Emerging Treatments for Hair Loss
In addition to the above treatments, others are gaining in popularity, and while unapproved, they are being utilized more and more as either standalone or additive treatments to those above. These include:
Platelet-Rich Plasma (PRP) is a treatment consisting of an injection of a patient’s own plasma (the liquid part of blood) that is rich in platelets (important in clotting and healing). PRP is not just used for stimulating hair growth. It is commonly used in sports injuries such as tendonitis and muscle and joint injuries, as well as to treat wrinkles on the face (more commonly known as a “vampire facial”). The nutrient-dense injection is thought to reduce hair loss in these patients while platelets provide healing growth factors that allow hair follicles to produce hair. Multiple treatments are typically required before patients begin to see results, and this method is considered more invasive than others previously mentioned. (5)
Microneedling is a treatment that harnesses the body’s own regenerative wound healing abilities. Using either a rolling device (a drum consisting of hundreds of tiny needles connected to a handle) or a pen device, tiny puncture wounds are made in the top layer of skin. The healing process follows which brings blood, nutrients, and growth factors to the area. During the process, hair follicles are stimulated to grow and mature, stimulating hair growth. The procedure can also be used to enhance drug absorption into the scalp, improving the effectiveness of existing treatments. More research is needed to determine how efficacious microneedling for hair growth is, but this option is gaining in popularity. (6)
Hair transplantation is a surgical approach to combat hair loss. In this technique, a surgeon takes hair follicles from areas of the scalp that are resistant to the effects of DHT such as the back of the head, and these are transplanted into areas of hair loss. The effectiveness of this procedure varies depending on differences in techniques and the skill level of the surgeon. For the most part, results are seen after 6 to 8 months, and other agents such as minoxidil sometimes need to be added to prevent further progression of the disease. (7)
Stem cell treatments for hair loss can be divided into 2 types:
Follicle-derived: This type of hair cloning involves harvesting hair follicles from a patient, growing them in a laboratory, and then re-implanting them across the affected areas of the scalp. This is still in its preclinical, experimental phase, with hair follicles currently being stored in a laboratory and grown in vitro. (8)
Adipose-derived: In this option, stem cells are obtained from fatty tissue through liposuction, conditioned, and then injected back into the scalp to induce hair growth. This type is actively practiced and has seen success in people fighting hair loss. (8)
Adipose-derived stem cells are also known as adipose-derived regenerative cells (ADRC). Adipose, or fat tissue, is the body’s largest store of stem cells. These cells are also relatively easy to obtain via liposuction versus bone marrow harvesting. As well, fat tissue contains inherent anti-androgen and anti-inflammatory properties, which helps to target the believed causes of androgenic alopecia. Combined with its ability to create new blood vessels (neovascularization), this treatment presents a promising venue to combat hair loss. (9)
A new combination therapy is being researched, which combines ADRC with platelet-rich plasma, known as autologous fat transfer with PRP (AFTP). PRP provides growth factors from platelets as well as promotes the growth of stem cells. Adding PRP to adipose tissue also helps to ensure better survival of the graft with easier application due to PRP somewhat “liquifying” fat tissue. (9)
New Hair Loss Treatments
Many treatment modalities are also constantly being looked at in new ways, whether that entails a different formulation of an existing treatment, a combination of treatments into one delivery system, or the addition of a new class of medication. Baldness research is continuing to provide new and interesting pathways to treat those suffering from hair loss!
Improving Minoxidil Absorption
Minoxidil is FDA-approved as a liquid and foam. These formulations limit side effects and allow for targeted treatments. The downside is that these products have low absorption and therefore can also have low efficacy.
Unfortunately, the issue isn’t easily resolved by simply using higher concentration products. Studies have shown that higher concentrations of minoxidil are no more effective than lower-dose FDA-approved options but cause far more side effects. Increasing absorption in an alternative way can help improve people’s response to minoxidil.
In order for topical minoxidil to work, it must be converted into its active form, minoxidil sulfate. This is done mostly by SULT1A1 enzymes found in the scalp.
SULT1A1 is a novel enzyme booster, meant to be used 5-10 minutes before applying minoxidil. When men with androgenic alopecia used both the enzyme booster and 5 percent minoxidil, 75 percent of them experienced hair regrowth after 60 days. Only 33 percent of men using minoxidil on their own saw the same effect. (10)
Minoxidil absorption may also improve when taken orally. While oral minoxidil is not FDA-approved as a hair loss treatment, it is not exactly new, either. Back in the 1980s, physicians noticed that an oral blood pressure medication, Loniten (brand name for oral minoxidil), was causing an interesting side effect: hair growth.
The FDA approved topical minoxidil as a treatment for hair loss in men in 1988 and followed up with approval for women in 1991. (2) This topical formulation was the mainstay of treatment for people with alopecia, as the oral form’s dose, starting at 5 milligrams, would often bring unwanted side effects. Currently, low-dose oral minoxidil is being trialed as a hair loss treatment, as doses as low as 1 milligram have been reported to cause hair growth.
A new formulation of low-dose oral minoxidil has shown success in females with androgenic alopecia and small studies have shown similar results in males. A 2019 clinical trial compared daily doses of 1-milligram oral minoxidil to daily applications of 5 percent topical minoxidil in females suffering from pattern hair loss. Over 24 weeks, this study showed a 12 percent increase in hair density in the oral minoxidil group compared to 7.2 percent in the topical group. This was found to be a statistically non-significant difference, meaning both formulations work as well as each other. This offers a possible alternative to those suffering from pattern hair loss who are seeking a non-topical treatment. (11)
Topical DHT Blockers and Microinjections
5α-reductase inhibitors like finasteride and dutasteride are usually used as oral medications. However, these oral drugs often come with systemic side effects, such as decreased libido, sexual dysfunction, and breast tissue enlargement in men. Reformulating these 5α-reductase inhibitors into topical products like lotions and creams allows them to produce a more targeted effect while reducing these unwanted side effects.
Dutasteride has a longer half-life and higher potency than finasteride in inhibiting 5α-reductase, reducing DHT by 90 percent. Unfortunately, this also means that side effects such as erectile dysfunction, decreased libido, etc. are just as likely for dutasteride users. (12)
Dutasteride microinjections are currently being studied as a way of providing local therapeutic action while minimizing side effects. In a 2017 study, 6 patients with pattern hair loss were treated over 9 months. They were given injections of 0.01 percent dutasteride at 3-month intervals. The dutasteride microinjections resulted in significant increases in hair density and hair diameter in all patients, with no adverse effects. (13)
A separate study evaluating 0.05 percent dutasteride injections showed increased hair density in 92.9 percent of patients receiving 7 injections spaced 1 week apart. Only 7.1 percent of people in the placebo group showed increased hair density. There were no significant differences in adverse effects between the two groups. (14)
Topical Finasteride Combination Treatments
Finasteride began being studied as a topical formulation to treat pattern hair loss in 1997, as an alternative to oral formulations. This treatment was safe to use in women as well, as finasteride applied topically provides far less absorption and therefore little to no systemic side effects compared to oral, which for this reason was reserved for men only. (15) Scientists have developed a new combination of topical 3 percent minoxidil plus topical 0.25 percent finasteride as one solution.
Researchers studied this combination in comparison to simply 3 percent minoxidil in 30 postmenopausal women with female pattern hair loss. By 24 weeks, they found the combination treatment to be superior to minoxidil alone in terms of hair diameter. The authors do note however that because some finasteride can be absorbed through the skin, this potential treatment should be reserved for post-menopausal women. (16)
Topical finasteride has also been combined with other hair loss treatments. NuH Hair is a new lotion that contains topical finasteride, dutasteride, and minoxidil! Combining these medications delivers triple-action against hair loss and was shown to stimulate hair growth within 3 months of use in one study assessing 15 patients with pattern hair loss.
Participants in the study were also given the option of using Rogaine foam, ketoconazole shampoo, and oral finasteride. The people who used NuH hair along with all three medications saw hair regrowth in 30 days! (17) More research is being done to assess the effectiveness of this new treatment, but tackling hair loss via three different pathways that are known to work individually appears to be a promising option.
Spironolactone and Minoxidil Combination Treatments
Spironolactone is an oral medication that is usually used to treat heart failure and high blood pressure. However, this drug also acts as a DHT blocker. A novel combination gel consisting of minoxidil 5 percent and spironolactone 1 percent gel was tested against either of these treatments alone in 60 patients, both male and female, with androgenic alopecia.
After 12 months, researchers found that while 90 percent of the minoxidil group and 80 percent of the spironolactone group showed hair growth, 100 percent of the combination group demonstrated improved hair growth! The idea behind this combination is to deliver a powerful combination therapy with decreased risk of side effects, as low-dose, topical spironolactone is thought to be well-tolerated compared to finasteride. (18)
In addition, researchers studied a combined therapy of oral minoxidil plus oral spironolactone in adolescent girls with female pattern hair loss aged 13 to 18. They found objective improvement in 5 out of 6 patients after 13 months. (19)
Hair Loss Research: Current Areas of Interest
In addition to the novel hair loss therapies mentioned, there are areas that researchers and pharmaceutical companies are pursuing in the quest to treat hair loss. The chart below shows hair loss treatments that are still completing clinical trials.
Hair Loss Research in Clinical Trials
COMPANY - PRODUCT
PHASE 1 (USA)
Next results in*
*FDAAA 801 states that all clinical trials must submit their results within 12 months of the date on which the final subject was examined or received an intervention. ‘Next results’ is estimated based on this law and the completion date listed on the clinical trial’s page.
Biosplice Therapeutics’ Wnt Booster SM04554
Biosplice Therapeutics, based in California, is researching a topical therapy for pattern baldness (SM04554) that targets the Wnt pathway, a cell signaling system. The Wnt pathway is heavily involved in cell cycling. By developing a drug to activate it at key moments, hair follicles can be “turned on.” If successful, this treatment can help to stimulate hair growth via the body’s own cellular function. (20,44)
RepliCel and Shiseido’s Autologous Cell Therapy RCH-01
RCH-01 is another therapy being trialed in the treatment of pattern hair loss. It represents a treatment known as “autologous cell therapy,” where a patient’s own cells are grown and reimplanted to achieve the desired effect.
The cells used in RCH-01 are known as dermal sheath cup (DSC) cells, which are the cells lost in androgenic alopecia. Implantation of these cells into the scalp has the potential to induce normal hair follicle function and produce hair growth. This research is being done by RepliCel, a Canadian regenerative medicine company, in collaboration with Shiseido, a Japanese cosmetics company. (21,22)
Follica’s Hair Follicle Neogenesis Device
Follica, headquartered in Boston, U.S.A., is trialing a proprietary medical device in combination with a topical growth formula to treat hair loss. Their method involves combining a topical medication with “micro-trauma” which is similar to microneedling. Their process aims to grow new hair follicles and stimulate growth where follicles already exist. (23)
Clacosterone, a topical solution used to treat acne, is also being researched as a hair loss treatment. Clacosterone (known as Winlevi®) is an FDA-approved drug used to treat acne. This medication is also being explored as a hair loss treatment. When used for pattern hair loss, this medication is known as Breezula®.
This androgen receptor blocking drug was developed by Cassiopea, an Italian pharmaceutical company. The androgen blocking effects of this drug are now being investigated for the treatment of androgenic alopecia in both men and women. (24)
A Chinese pharmaceutical company, Kintor, is trialing its own androgen receptor blocker, known as pyrilutamide or KX-826. It is currently being studied in both China and the United States. Like clacosterone, it is also being studied separately as a treatment for acne vulgaris. (25)
In addition, Kintor has entered phase 1 trials of another compound, GT20029, which is an androgen receptor degrader. It is also being trialed for the treatment of alopecia and acne vulgaris. (25)
Energenesis Biomedical’s Cell Booster ENERGI-F701
Energenesis Biomedical, based in Taiwan, is investigating ENERGI-F701. This is a topical treatment meant to boost the cellular activity of specific enzymes to increase hair growth. ENERGI-F701 is currently being studied in phase 2 trials to assess its efficacy in treating female pattern hair loss. (26)
TechnoDerma’s Topical Small Molecule Drug
A novel topical “small molecule” therapy known as TDM-105795 is currently being trialed by the Chinese biotechnology company, TechnoDerma. While not much is known about the mechanism of action of this particular drug, phase 1 clinical trials are underway to assess the safety and adequate dosing of this “cutting-edge technology”, according to the company. (27)
Medical Life Care Planners’ Varin and CBD-Rich Hemp Oil
Medical Life Care Planners, LLC, a medical cost projection company that calculates life plans and medical costs for injury settlements based in the USA, are approaching the treatment of hair loss from another direction. They are currently recruiting for phase 1 trials, testing a topical hemp oil to treat androgenic alopecia, following a similar successful trial. (28)
Hair follicles contain endocannabinoid system receptors which are believed to inhibit hair growth. This company is assessing the utility of this topical hemp oil to inhibit these receptors and induce hair growth via specific components of hemp oil called varins and CBD. These are specific components unlike those found in commonly seen hemp products. (28)
What Can We Learn From the Latest in Hair Loss Research?
The above studies and trials provide interesting insights into not only the future of hair loss treatment, but our understanding of how hair growth and hair loss happen. Every year great strides have been made in the science of hair growth, and these studies provide us with an opportunity to look in-depth at how they chose to pursue their unique avenue of combatting hair loss.
The Wnt Pathway Regulates Hair Regrowth
Research into utilizing the Wnt pathway for hair loss centers on the understanding of cell biology. Simply put, the Wnt signaling pathway is important for allowing certain signals into cells, but not others. This is done through specific cell surface receptors, and depending on the signal, cells can be stimulated to produce or stop producing proteins.
The development of multiple tissues depends on the Wnt signaling pathway. Biosplice Therapeutics’s research is based on Wnt signaling — specifically, the way it initiates and maintains the anagen phase of the hair growth cycle. This is the phase when hair follicle cells rapidly divide and grow and new hairs are formed. Wnt activation also causes the development of new hair follicles, and the reduction of Wnt signaling is associated with progressive hair loss. (29)
SM04554 is an experimental, topical Wnt modulator being studied by Biosplice, and is currently undergoing phase 3 trials after proving safety and efficacy in Phases 1 and 2. In these studies, 49 patients were split between 0.15 percent, 0.25 percent, and placebo treatments.
After an active treatment phase of 90 days, both treatment groups saw statistically significant results over the placebo group, with more increased hair counts in the stronger treatment group (0.25 percent). After another 51 days of follow-up, both treatment groups had roughly equivalent results. Surprisingly, the lower strength treatment group saw a greater increase in both vellus hair count, which are shorter and lighter hairs sometimes called “baby hairs”, and terminal hairs which are the thicker, longer hairs. (30)
A second phase 2 study investigated 300 patients split into 3 groups, once again with one group receiving 0.15 percent SM04554 solution, one with 0.25 percent solution, and one with simply placebo. Subjects were investigated for clinical and imaging outcomes at 45, 90, and 135 days.
By day 135, hair counts improved in treatment groups (10.1 per cm² for the 0.15 percent group, 7.7 per cm² for the 0.25 percent group) and decreased in the control group (-2.8 per cm²). This was true as well for hair density (336.4 µm per cm² in the 0.15 percent group, 281.7 µm per cm² in the 0.25 percent group, and -418.7 µm per cm² in the control group).
In terms of change from baseline, the 0.15 percent group had the greatest improvement, showing what scientists term the “goldilocks effect”. In this phenomenon, a “more is better” approach is not always best, as the group with the highest dosage wasn’t the one with the most improvements. Instead, another group with a lower dosage had better results. Sometimes, a medication’s dosage needs to be “just right” to work. (30)
Dermal Sheath Cells Support and Stimulate Hair Follicles
Dermal sheath cells are found in the base of hair follicles. RepliCel is using these cells in their study to combat hair loss. In their technique, dermal sheath cells are isolated from a patient’s own hair sample. These cells are then grown in a laboratory and reimplanted into areas of hair loss. The idea behind this approach is that dermal sheath cells can both revert resting hair follicles into actively growing (anagen) hair, as well as produce new, fully functional hair follicles.
RCH-01 is RepliCel’s autologous cell therapy that’s now entering phase 3 trials. It seeks to improve hair growth in those suffering from pattern hair loss. In their phase 2 study, 50 men and 15 women with pattern hair loss were randomly assigned to treatment with a one-time injection of 7.5×106, 1.5×106, or 3.0×105 dermal sheath cells, or a placebo. They were then followed up at 3, 6, 9, and 12 months. Similar to SM04554, the lowest dose injection showed statistically significant improvement in cumulative hair diameter and total hair density compared to higher doses. Adverse effects were mild and well-tolerated and included swelling, redness, and minor bleeding. (31)
Combining Microneedling With Topical Treatments
Another treatment modality utilizing a clinical device is also being examined. Follica’s proprietary device, the Hair Follicle Neogenesis (HFN) device, along with an unspecified topical treatment, was investigated in a phase 2b trial to determine efficacy in a small group of patients suffering from androgenic alopecia. This device is meant to be used in-office as a 5-minute treatment option to limit downtime.
In this study, 48 patients with moderate grades of pattern hair loss were treated with the device, followed by a topical compound. No serious adverse effects were reported, while the combination therapy demonstrated a 44 percent improvement in visible hair count after 3 months. The HFN device functions very similarly to a microneedling device, introducing hundreds of tiny perforations in the upper layer of skin to promote collagen and growth factor release. (32)
Targeting Androgen Receptors in Different Ways
Androgenic alopecia is known to be hormone-driven, with DHT as the main culprit. DHT is known as an androgen or male sex hormone. These hormones perform their functions by interacting with specific receptors made uniquely for them, known as androgen receptors. Research into combatting hair loss therefore includes the investigation of medications that can block the androgen receptor, therefore mitigating DHT’s effects. Both Cassiopea and Kintor are trialing their own specific drugs for this purpose, but their modes of action are similar.
Cassiopea’s drug Breezula®, also known as clascoterone, is a topical formulation that has performed well in phase 2 trials for safety and efficacy. In their trial, 344 men with mild to moderate pattern hair loss were randomly assigned to one of 5 groups: 2.5 percent solution twice daily; 5.0 percent solution twice daily; 7.5 percent solution twice daily; 7.5 percent solution once a day, and vehicle (placebo) solution twice daily.
The researchers found that every treatment group exhibited a statistically significant increase in hair counts compared to members of the placebo group, who had decreased hair counts. The largest increase was in the 7.5 percent solution twice daily group. It also demonstrated a strong safety profile with no serious adverse events reported in any treatment group. This shows promise in treating those with mild to moderate androgenic alopecia while limiting adverse reactions. (33)
Kintor’s second trial, studying the effects of GT20029, approaches the DHT avenue in a different way. Rather than a drug that competes with DHT and blocks the androgen receptor, this medication degrades the receptor itself, leaving nothing for DHT to bind to and exert its effects with. GT20029 is what is known as a proteolysis-targeting chimera (PROTAC), which simply means it is designed to target and bind to a specific protein, and “label” it for degradation by the body’s immune system. Phase 1 clinical trials are currently underway to assess this drug’s safety and tolerability in humans. (25)
Boosting Enzymes Prolongs the Hair Growth Cycle
ENERGI-F701 is an experimental treatment aimed at the biochemical processes which take place in the hair follicle cells. According to the Energenesis website, this compound increases the activity of AMPK, or AMP-activated protein kinase. Put simply, this is an enzyme that controls a cell’s ability to utilize glucose and fatty acids to produce energy when stores are low. By increasing ATP, the energy used by cells, this experimental treatment aims to prolong the hair cycle by expanding energy uptake by cells. (26)
Targeting Hair Follicles’ Endocannabinoid System
Endocannabinoid system receptors are found in skin and hair tissue, and since their discovery they are believed to act as regulators of hair growth cycles, inhibiting the process when activated. Specifically, cannabinoid type 1 receptors (CB1) are found in high density in hair follicle cells. Cannabidiol, or CBD, is what is known as a “negative allosteric modulator” of these receptors, meaning it binds to CB1 and changes its normal function.
In addition, the cycle of hair follicle growth is controlled by vanilloid receptor 1 (TRPV1), and a receptor of the same family, TRPV4, can cause premature hair shedding when cannabidiol levels are too high. Topical cannabidiol is an inhibitor of CB1, and an agonist of TRPV1 and TRPV4. As well, cannabidiol increases Wnt signaling, which as discussed above is important for hair growth via protein synthesis and differentiation of cells into functional hair follicles.
In a study published in 2021, Medical Life Care Planners explored a new hair loss treatment targeting endocannabinoid system receptors. 35 patients with pattern hair loss underwent treatment with a topical hemp oil consisting of roughly 3-4 milligrams of cannabidiol per day for 6 months. After the study, they found that all subjects had some hair regrowth, with a statistically significant 93.5 percent growth on average for hair count in a defined area of hair loss. There were also no reported side effects. (34)
Which Clinical Trial for Hair Loss Shows the Most Promise?
Each of these treatments appears to show promise in one form or another. For some, such as the hemp oil formulation, Kintor’s androgen receptor degrader, or TechnoDerma’s small molecule system, it is still too early to tell as these clinical trials are still in their infancy. Similarly, Energenesis’ phase 2 trial results are not yet available, making it difficult to properly ascertain its potential.
Cassiopea’s Breezula® and Kintor’s KX-826 phase 2 trials have been successful, indicating at the very least comparable efficacy to the currently available treatments for pattern hair loss. Both companies are expecting to begin phase 3 trials soon, and larger-scale results will shine even more light on the role of androgen receptor blockers in androgenic alopecia.
Follica’s device has also shown 44 percent hair growth in its recent phase 2b trial, indicating its place as a contender in this booming space. Biosplice and RepliCel’s successful phase 2 trials have allowed them to enter phase 3, with Biosplice expected to release their results by the end of 2021. If larger-scale trials show further success, these treatments will likely enter the mainstream of pattern hair loss treatment.
What Is Next in Hair Loss Research?
Even further up the research pipeline are experimental hair growth therapies that are yet to begin clinical trials. These cutting-edge technologies are still in experimental, preclinical phases. They are either seeking or planning to begin clinical trials soon, and offer key insights into interesting approaches to treating hair loss.
Preclinical Hair Loss Research
COMPANY / PRODUCT
Clinical trial starts in
Dermal Papilla Cell Transplant Therapy
Epibiotech, a Korean-based research and development group, is examining the effects of dermal papilla cell therapy. Dermal papilla cells are found at the base of the hair follicle and are important for hair growth and cycling.
Similar to RepliCel’s dermal sheath cell therapy, Epibiotech is looking into obtaining these cells, replicating them, and injecting them back into areas of hair loss to stimulate the formation and growth of hair in areas of hair loss. They are now able to create samples of these cells for clinical and non-clinical purposes, and phase 1 clinical trials to assess safety and efficacy are scheduled to begin in 2022. (35)
Another company working in the dermal papilla space is HairClone, based in the United Kingdom. Their research focuses on obtaining hair follicles, which are then cryopreserved in the world’s first “Hair Bank”. These cells can then be retrieved when needed, grown and multiplied in the laboratory, and injected into areas of hair loss to induce new follicle formation.
Dermal papilla cells are reduced in certain hairs and conditions leading to hair thinning and loss. HairClone is therefore researching the utility and ability to create a virtually limitless source of implantable hair follicles. Clinical trials are still years away, but in the meantime, they are planning to offer a cell expansion service starting in 2022, where a patient’s hair cells can be multiplied and transplanted as an unlicensed procedure prior to clinical trials. (36)
TissUse and J. Hewitt’s Smart Hair Transplant System
In 2019, TissUse, a German biotechnology company, granted distribution and development rights to Japanese biopharmaceutical firm J. Hewitt for their Smart Hair Transplant (SHT) system. This agreement allows J. Hewitt to develop hair regeneration therapies, leveraging this technology and the expertise of TissUse. (37)
The Smart Hair Transplant system functions similarly to RepliCel’s RCH-01 and to Epibiotech’s system. It works by obtaining about 30 hairs from the back of the scalp to retrieve dermal papilla cells. These cells are then cultured to form about 10,000 “neo-papillae”, which can be injected back into the patient’s scalp. Clinical trials were delayed due to the Covid-19 pandemic, but are now scheduled to begin in 2022. (37,38)
The Riken Institute’s HSFCs for Cyclical Hair Regeneration
In February 2021, Dr. Takashi Tsuji of the Riken Institute released a paper in Nature Scientific Reports titled “Expansion and characterization of epithelial stem cells with potential for cyclical hair regeneration”. In this paper, Tsuji developed a new culturing method using hair follicle-resident epithelial stem cells (HFSCs). Using this unique culturing technique, these stem cells can grow into functioning hair follicles capable of following the hair growth cycle just like a natural hair follicle! (39)
The Riken Institute hopes that these cells will be the ideal type to harvest, grow, and reimplant in people suffering from hair loss. They ultimately intend to clone these cells and implant them, creating cycling hair follicles. Phase 1 trials are expected to begin in 2022. (40)
Stemson Therapeutics’ Folliculogenic Cells
Human beings possess induced pluripotent stem cells (iPSCs), which are stem cells that have the unique ability to replicate and differentiate into almost any type of tissue. Stemson Therapeutics, headquartered in San Diego, California, is attempting to utilize these cells to produce “folliculogenic cells”, or cells that are responsible for the formation and growth of hair follicles.
This company has created a method to obtain regular cells from a patient, generate pluripotent stem cells from them, and differentiate these stem cells into folliculogenic cells. They have also created a cellular scaffold to support these growing hair follicles. The next step in their research is to implement their system in clinical trials, which are expected to begin by 2024. (41,45)
Seeking a Cure for Baldness
Baldness is an issue that has many causes and can stem from many conditions. As such, a “cure” for baldness does not exist, and research into curing baldness is still in its infancy.
One realm of potential promise is in the area of gene editing. CRISPR-Cas9 (clustered regularly interspaced short palindromic sequences), is a technology that is used to edit genes within organisms!
CRISPR has been utilized for basic scientific research, treatment of diseases, and the development of biotechnology. Its utility for treating hair loss has yet to be fully explored. In treating androgenic alopecia, for example, it could be used to decrease responsiveness to DHT, increase the expression of pro-growth proteins such as collagen, biotin, vascular endothelial growth factor (VEGF), among many other possibilities!
CRISPR is typically delivered into cells via viruses. But recently, a team of researchers developed a novel microbubble-nanoliposomal CRISPR delivery system that is activated by ultrasound! To test their new system, they implemented it on a mouse model for androgenic alopecia. These mice had their backs removed of hair and were given testosterone to mimic this form of hair loss.
The mice received a CRISPR-Cas9 molecule designed to “snip” (or deactivate) the SRD5A2 gene. This gene is responsible for coding an enzyme that converts testosterone to DHT. Once activated, they found that SRD5A2 production decreased by 70 percent, and up to 90 percent of hair regrowth was achieved! (42,46) CRISPR-Cas9 technology is a breakthrough, and it may just hold the cure for baldness!
Although it’s not exactly a cure, advances in stem cell research could also soon make baldness a thing of the past. A study published in 2020 successfully demonstrated the ability to grow functional skin “organoids”, complete with hair follicles, from pluripotent stem cells in mice! (43) Pluripotent stem cells can duplicate but have not yet specialized. They therefore have the potential to develop into any cell of an adult body.
The researchers from this study used specialized growing methods to coax these cells into developing layers of skin equivalent to those found in a second-trimester human fetus, which includes nerves, specialized touch-sensitive cells, and hair follicles. What’s more, they then grafted these organoids onto nude mice. The organoids formed into planar, hair-bearing skin! (43)
The ability to grow complete skin means the ability to also grow functional hair follicles. And if hair follicles can be created from cells found anywhere on the body, people could grow a virtually unlimited supply. In theory, they could always have full heads of hair.
Of course, implementing this in people would probably require going into a clinic for a small procedure every few years. Implanting new cells will always require minor surgery, whereas CRISPR gene editing can be done without any surgical interventions. Nonetheless, it means baldness could eventually become a problem of the past and easily treatable at any point in life!
What We’ve Recently Learned About Hair Loss
The last few years have seen an incredible expansion of hair loss treatment options, with major advancements in cutting-edge hair science research. The future looks bright and hair loss may soon be a thing of the past.
What We Learned in 2020 About Hair Loss
In 2020, well-known hair loss treatments were redesigned and tested in interesting ways, such as dutasteride microinjections and low-dose oral minoxidil. Interesting combinations, like oral minoxidil with spironolactone and topical finasteride with minoxidil, were also used to combat androgenic alopecia.
2020 also saw successful clinical trials for dermal sheath cup cells and for Follica’s microneedling-type device. An ultrasound-activated CRISPR delivery system with the potential to combat androgenic alopecia was developed as well!
What We Learned in 2021 About Hair Loss
2021 saw a great deal of boundary-pushing in the field of hair loss and ways to treat it. This year, we saw how boosting the SULT1A1 enzyme greatly improves minoxidil’s efficacy as a hair growth treatment. The combination of minoxidil and spironolactone was again tested, but this time in adolescent girls, showing continued success. A study reviewing the utility of oral minoxidil was published, showcasing it as an ongoing, effective, and well-tolerated treatment option.
In 2021, we also saw the expansion of several research streams and experimental treatments such as topical hemp oil, androgen receptor blockers, androgen receptor degraders, topical small molecule therapy, cell enzyme boosters, and more! Stem cell treatments made significant strides this year, with The Riken Institute and Stemson Therapeutics preparing for clinical trials. Autologous cell transplant therapies created by HairClone, TissUse, Epibiotech, and RepliCel have also been expanded and trials continue to progress.
The possibilities in treating hair loss continue to grow due to the continued research and development of exciting new therapies. As the year draws to a close, we will keep a close eye on Biosplice’s Wnt agonist treatment. They completed their phase 3 trials and are expected to release their results by the end of 2021.
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