Category Archives: Wound Healing

Cassiopea, Drew Brees and FAK Inhibitors

An interesting week in hair loss news warrants a wide ranging post.

Cassiopea Topline Results for Female Hair Loss

We are eagerly awaiting Cassiopea (Italy)’s Phase 3 Trials for Breezula for androgenetic alopecia (male pattern hair loss). However, several days ago, the company posted an encouraging update on its Phase 2 proof of concept trial for clascoterone use in female hair loss patients. Clascoterone is a topical androgen receptor inhibitor, and its hair growth benefits are almost certainly going to be greater in men.

The trials encompassed 293 women aged between 18-55. The were split into four groups: 5.0% and 7.5% twice daily application of clascoterone solution; versus twice daily 2% Minoxidil or vehicle. Only the subgroup with women less than 30 years of age receiving twice daily application of 5% clascoterone solution showed statistically significant differences from baseline in  total hair count at month 6. No safety issues were detected.

Cassiopea Clascoterone Hair Loss
Cassiopea pipeline for clascoterone to treat hair loss.

Drew Brees Hair Transplant

Drew Brees is a superstar quarterback in American Football (NFL). The 42-year old retired in 2021 after a stellar career. He was also well known for his early hair loss and receding hairline…until this week. Looks like he got a hair transplant with excellent results.

Drew Brees Hair Transplant
Drew Brees hair before and after.

I have discussed numerous other celebrity hair transplant results over the years. Among the most famous athletes who got hair transplants include Wayne Rooney and Brian Urlacher. Possibly also Lebron James.

FAK Inhibitor for Hair Loss

I saved the most important news for last. In recent days, a few people discussed this Stanford University research (first posted by “DrPhil”) on our hair loss chat.

FAK Inhibitor Hair Growth
FAK inhibitor skin healing and hair follicle regrowth at 180 days. Source: Nature Communications.

The researchers found that blocking mechanical signaling via FAK  (focal adhesion kinase) inhibition promotes regenerative skin healing. Moreover, this restored skin includes hair follicle regrowth in addition to normal collagen fiber architecture. Most importantly, this hair regrowth was shows in both mice and pigs.

This is significant because porcine skin has striking similarities to human skin. The researchers used a pharmacologic inhibitor of FAK (FAKI) called VS-6062. This pharmacologic blockade of mechanical signaling resulted in skin with less scar formation and more hair.

The FAK was delivered to wounded skin using a biodegradable and biocompatible hydrogel scaffold.

Better than Verteporfin?

Per @DrPhil on our chat:

“This VS-6062 FAK inhibitor does the same thing as verteporfin, but it inhibits a target which is upstream of YAP. Verteporfin only inhibits YAP, while VS-6062 inhibits FAK (which controls YAP) and also other targets. FAK inhibitors can also be applied topically, with no injections required. Moreover, VS-6062 has already gone through Phase 1 and Phase 2 clinical trials to treat cancer.”

According the Stanford team, porcine serum FAKI concentrations following local treatment were almost undetectable. In fact they were less than 1% of the maximum tolerated human dose observed in a previous Phase 1 clinical trial. So safety issues are likely to be nonexistent in my opinion.

Interestingly, the earlier verteporfin research was also undertaken at Stanford, via the Longaker Lab.

Skin Regeneration, Wound Healing and Hair Growth

The most “natural” way of regrowing lost hair is via wounding or intentional injury. Hence the massive popularity of at-home microneedling and dermarolling for hair growth.

However, no-one truly understands the biology of wound healing spurred new hair follicle growth. We have been waiting for 15 years for Follica to come through.

I am updating this post because an important new study on wound healing and hair follicle mesenchymal stem cells was published in June 2021. The researchers behind this paper concluded the following:

“During wound healing, dermal papilla (DP) and dermal sheath (DS) cells move towards the wound, but do not directly participate in follicle neogenesis.”

They further elaborate that follicle neogenesis during wound healing is a genuine de-novo process. The new follicle formation does not rely on any preexisting components from preexisting follicles.

October 24, 2020

Wound Healing and Hair Follicle Growth

Two recent papers published important new findings in regards to wound healing and skin regeneration.

Wound healing via skin regeneration is often accompanied by hair follicle regeneration. Or even by brand new hair follicle neogenesis (e.g., Follica). Note that this hair growth after wounding phenomenon was even being researched in the 1950s and 1960s.

Thousands of hair loss sufferers around the world are trying out at-home microneedling and dermarolling. Many of them have seen significant success, although one has to be careful with this type of scalp self-injury. On our hair loss chat, the most interesting recent discussion is around wounding depth levels.

Human embryonic and neonatal skin has the potential to regenerate after wounding. This includes fully functioning hair follicles. However, adult skin no longer has such regenerative capabilities. Researchers have been trying for years to find ways to coax salamander-like regenerative powers in humans. If not for whole limbs, at least for hair growing skin to cover baldness for our sake.

New Studies on Skin Regeneration and Wound Healing

1) In September 2020, a team that included Dr. Jeff Biernaskie published a study on the regenerative potential of dermal fibroblasts during wound healing. They identified a specific population of progenitor cells that reside within the dermis and which aid in wound healing.

Skin Regeneration Regulators
Skin Regeneration Regulators. Source: Bernaskie Lab GitHub.

The research is shared on GitHub. Also see Biernaskie Lab. According to the findings, Runx1, retinoic acid, and Hic1 control mesenchymal regenerative capabilities.

According to this summary, Dr. Biernaskie (whose work I have covered in the past) said that they have shown the following:

“You can alter the wound environment with drugs, or modify the genetics of these progenitor cells directly. Both are sufficient to change their behavior during wound healing. And that can have really quite impressive effects on healing that includes regeneration of new hair follicles, glands and fat within the wounded skin.” 

“It suggests that the adult wound-responsive cells do in fact harbor a latent regenerative capacity, it just simply needs to be unmasked.”

2) Also in September 2020, a new study from the University of Washington identified Wnt transcription factor Lymphoid enhancer-binding factor 1 (LEF1) as the key factor in adult skin regeneration.

LEF1 gene expression in fibroblasts has the potential in adult skin to repair itself like the skin of a newborn baby. This skin  can also grow new hair follicles.

Interview with lead author Dr. Ryan Driskell.

“We identified a genetic factor that allows adult skin to repair itself like the skin of a newborn baby.”

Hair, Skin and Wounds all Interconnected

While researching for this post, I could not believe the number of diverse past posts that I have written on this blog that have focused on skin regeneration, wound healing and hair formation.

Regenerating hair follicle after wounding.
Wound induced single hair follicle neogenesis in a bald old man.

Renowned hair loss researchers such as Dr. George Cotsarelis, Dr. Luis Garza, Dr. Elaine Fuchs and Dr. Mayumi Ito have all also conducted frequent research on skin regeneration. I have discussed their work in past posts if you search for their names.

My gut feeling is that whenever there is a fully effective cure for hair loss, there is a strong likelihood that there will also be a cure for quality skin regeneration.

Skinregeneration.org

The authors of the second study that I linked to earlier have started a new site called skinregeneration.org. The site’s mission is to provide a platform for scientists to easily query large datasets that focus on skin wounding and scarring repair.

For further information, see the Driskell Laboratory site at Washington State University.

Skin Gun and Spray-On Skin

It seems like the technology to repair skin has improved significantly during the past decade. There is an especially unmet need when it comes to treating skin that has been burnt badly.

One of the technologies that I used to very curious about is the skin gun that was widely hyped in 2011. I have not heard much about this in recent years. RenovaCare acquired the technology in 2013. The company’s skin gun and spray-on stem cells for wound healing are trademarked under the names SkinGun™ and CellMist™.