Fibroblast Growth Factors and Hair Growth

I have previously covered different fibroblast growth factors (FGFs) and their impact on hair growth. This post is a comprehensive summary of the key FGFs (cell signaling proteins) involved in hair follicle cycling.

Fibrobasts Growth Factors and Hair Growth

There exist 23 members of the FGF gene family, each identified by a number at the end. At least 5 of these fibroblast growth factors have significant impact upon hair growth. Usually via a modulation of the Wnt/β-Catenin pathway and Sonic hedgehog (Shh) expression. The fibroblast growth factor receptor family has 4 members,

FGF1, FGF2 and FGF10

FGF1, FGF2 and FGF10 have some positive impact on hair growth, although the research is limited. A Chinese study from 2015 found that FGF-1, FGF-2, and FGF-10 fibroblast growth factors promote hair growth. They do so by inducing and extending the anagen growth phase of hair follicle cycling.

A South Korean study from 2016 found that arachidonic acid increased the expression of FGF-10 (and FGF-7). This in turn promoted hair growth.

A Japanese study from 2016 concluded that FGF2 (also known as “basic fibroblast growth factor” or bFGF) seems to have a positive impact on hair growth. Interestingly, when I interviewed Dr. Malcolm Xing, he mentioned that FGF-2 is the preferred growth factor used at this clinic for his work purposes.

FGF5

On this blog, I have covered FGF5 more than any other fibroblast growth factor. Interestingly, this particular growth factor needs to be inhibited in order to promote hair growth.

Evolis Shampoo.
Evolis Shampoo to inhibit FGF5.

An Australian company named Cellmid has been very successful at selling its Evolis line of products. See the science behind their FGF5 inhibiting concept here and in the video below. On Amazon, their FGF5 inhibiting shampoo currently has an average rating of 4.1 out of 4.5. Cellmid seems to be doing well in spite of recent challenges.

The company’s products contain natural botanicals that have been shown to inhibit FGF-5. For example, one of the ingredients is Sanguisorba Officinalis Root Extract, known to reduce FGF5 and prolong the anagen hair growth cycle. A related Japanese patent.

FGF7

FGF7 (also called keratinocyte growth factor, or KGF) is required for hair growth. The well known hair loss researcher Dr. Elaine Fuchs co-authored an important study on FGF-7, hair development and wound healing in 1995.

A 2000 study found keratinocyte growth factor to be an important endogenous mediator of hair follicle growth. Histogen’s now discontinued Hair Stimulating Complex product included KGF as one of the key hair growth factors.

FGF9

An important 2013 mice study from U Penn found that FGF9 induces hair growth after wounding. Dr. George Cotsarelis was a co-author. More here. Reducing FGF9 expression decreased hair follicle formation. In contrast, over-expressing FGF5 led to a two to three-fold increase in the number of new hair follicles.

The researchers think that using FGF9 to treat wounds in people can also help regrow hair. Human skin tends to scar and not regenerate any hair after suffering injury, In contrast, mice skin is much better at also regrowing hair after injury.

Follica licensed the intellectual property rights soon after the study was published. The actual 2009 patent can be seen here. It seems like there exists a window of opportunity after wounding during which:

“The FGF9 pathway could be modulated to potentiate hair neogenesis”.

Cellcurin Topical Fibroblast Growth Factor 9

Interestingly, a 2019 study from South Korea tested a trademarked cocktail containing topical FGF9 (Cellcurin). They used this growth factor cocktail (GFC) in combination with microneedling on patients with androgenetic alopecia. The results (see below image) indicate Cellcurin to have a positive impact on hair growth and follicle thickness. A related article also mentions the addition of NMN.

Fibroblast Growth Factors.
Fibroblast Growth Factor 9 for hair growth. Source: Global Dermatology.

I hope someone can make a topical cocktail of most of the above fibroblast growth factors. At the very least, maybe this will reduce hair loss drastically.

Kintor Pharmaceutical from China

Kintor Pharmaceutical (China) is definitely the real deal. And they are moving faster than any other company that I have ever seen in the hair loss industry.

Update: July 11, 2021 — The US FDA just approved Kintor’s Phase II clinical trial for Pyrilutamide (KX-826) to treat androgenetic alopecia. Note that the company’s trials in China are already mid-way through Phase II per their pipeline page.

They area also working on another hair loss product named GT200029 that is an “AR-PROTAC” compound. Its Phase 1 trials will start in China this month.

April 15, 2021

Kintor Pharma: AR Antagonist and AR Degrader

Earlier today, it was announced that Kintor received approval in China to begin clinical trials for GT20029. This product will be in tincture or gel format, and will be tested for the treatment of androgenetic alopecia and acne.

  • The GT20029 product is an androgen receptor degrader (AR Degrader). It is developed using Kintor’s proprietary Proteolysis Targeting Chimera (PROTAC) platform. According to the press release, this is the world’s first topical androgen receptor (AR) compound (AR-PROTAC) to enter clinical trials. GT20029 degrades the AR protein via the E3 ubiquitin ligase pathway. During preclinical studies, GT20029 did not cause any notable side effects or systemic drug accumulation.
  • Note that Kintor’s main product for treating male pattern hair loss is KX-826 (Pyrilutamide) and is an androgen receptor antagonist (AR Antagonist). I covered the latter in prior updates to this post if you read till the end. KX-826 is currently in Phase 2 clinical trials in China and in Phase 1 trials in the US.

Note that Cassiopea’s Breezula (Clascoterone) is an AR antagonist that is well ahead of KX-826 when it comes to clinical trial stage. Kintor’s website has a very interesting article discussing both AR antagonist products and hair loss in China in general.

Make sure to also read my related past post on destroying the androgen receptor to reverse hair loss.

Feb 2, 2021

Clinical Trial Status

Kintor’s investigational new drug (IND) application of GT20029 for androgenetic alopecia and acne vulgaris was accepted by the National Medical Products Administration (NMPA) of China.

Kintor has moved forward with its trials faster than any other hair loss company. I am glad to see a Chinese company finally entering the hair loss cure market. Scientific and technological progress seem to happen faster in China than in the west. Hopefully, clinical trials for hair loss products will follow the same pattern.

Side note: In July 2020, Kintor and Applied Biology (US) collaborated on using Proxalutamide for the Treatment of COVID-19. There is a school of thought that suggests anti-androgens could help reduce Coronavirus fatalities. To date, more men have died from the disease then have women.

Below is the pipeline from Kintor’s website:

Kintor Pharmaceutical Pyrilutamide Pipeline
Kintor Pharmaceutical Pyrilutamide Androgenetic Alopecia Pipeline.

 

Kintor Pharmaceutical (China) also recently completed the enrollment of 120 patients in its Phase II clinical trials for Pyrilutamide for hair loss. See the bottom half of this post for my original discussion on Kintor. Their stock is traded on the Hong Kong Hang Seng Index.

Key quote from CEO Dr. Youzhi Tong:

“We will accelerate the progress of its phase II/III clinical study so as to bring benefits to the people suffering from alopecia as soon as possible.”

May 26, 2020

A new Chinese company named Kintor Pharmaceutical is working on an interesting hair loss drug called Pyrilutamide . It is extremely rare to hear about any Chinese company involved in hair loss cure research. Very strange, considering the country’s rapid pace of scientific advancement and massive population. Moreover, Chinese men and women are nowadays balding at much faster rates than in the past.

Update: August 4, 2020 — Phase Ib trials are now complete.

Kintor Pharmaceutical and Hair Loss

Four days ago, China-based Kintor Pharmaceutical (also known as Suzhou Kintor Pharmaceuticals) got significant Chinese media coverage. This interest was related to the company’s prostate cancer, breast cancer and hair loss drugs.

Earlier this month, Kintor Pharmaceutical also had a very successful IPO in Hong Kong.

While the company’s main focus seems to be its prostate cancer and breast cancer drugs, its androgenetic alopecia drug trials are also advancing rapidly. Their main androgen receptor blocking drug candidate is called Pyrilutamide (KX-826) and it is applied to the scalp topically. The company’s Proxalutamide drug slows or stops cancer cell growth by entirely inhibiting androgens.

Pyrilutamide

The one disappointing news is that Kintor aims to take on Johnson & Johnson’s Minoxidil. This could mean that topical Pyrilutamide is unlikely to be much better than Minoxidil. I hope I am wrong. Recently completed phase one trials in China proved that Pyrilutamide is safe and causes no major side effects in humans.

Kintor is currently conducting phase 2 clinical trials for Pyrilutamide on 160 men in China, and phase 1 trials on 30 men in the US. Phase 3 trials on 600 people in China, the US and Japan are planned for as soon as 2021. I would guess that the US FDA and Japanese PMDA will never accept Phase 2 results from China as any kind of proof to proceed to Phase 3 trials in the US and Japan.

So how can the company proceed so fast in the US and Japan?