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FDA approved drug Verteporfin found to fully regenerate skin, including hair follicles


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This research was just published in the past few weeks.

TL;DR: A very safe FDA approved drug was found to regenerate skin scarlessly with all the dermal appendages, including hair follicles. It regenerates skin on mice and pigs. Clinical trials on humans are planned to start this year, however, Verteporfin could be used off-label right now. The main question that needs to be answered is whether it will regenerate terminal scalp hair when used on the scalp after wounding.

Most researchers don't care about hair loss, so we could sit on a working cure for years waiting for trials to be conducted to test it.

For context, read the article from The New York Times here:
https://www.nytimes.com/2021/04/22/health/surgery-scar.html
Press release from Stanford University:
https://med.stanford.edu/news/all-news/2021/04/drug-enables-healing-without-scarring.html
Article relating it to hair loss:
https://www.folliclethought.com/verteporfin-could-create-scarless-hair-transplant-surgery/
Research paper:
https://science.sciencemag.org/content/372/6540/eaba2374

Summary:

  • The research paper [1] describes the mechanisms of scar formation in skin and a simple procedure to achieve full skin regeneration using a very safe FDA approved drug, Verteporfin. Full skin regeneration here refers to skin indistinguishable from normal skin with all the dermal appendages, including hair follicles. According to the paper, it is possible to achieve full skin regeneration by preventing a type of skin cell (ENF) from giving rise to another type of skin cell (EPF) that causes scarring during wound healing. The way Verteporfin does this is by blocking mechanotransduction signaling, i.e. the ability of cells to sense mechanical forces.
  • The studies were conducted on mice, but according to this article from The New York Times [2], it also works on pigs. Quoting from the article: "The study involved mice, but the researchers, Dr. Michael Longaker, Stanford’s vice chair of surgery, and Geoffrey Gurtner, Stanford’s vice president of surgery for innovation, have now moved on to pigs, whose skin is closest to that of humans. With these new subjects, the surgeons made an incision as wide as a thumb and five inches long. When they sutured the cut and injected Verteporfin around the edge, there was dramatically less scarring."
  • The procedure on mice involved, first, creating a wound using a skin biopsy punch around 4mm in diameter. After wounding, inject 30 μL of Verteporfin (1 mg/mL) [3] around the edges of the wound. Relevant here is that repeated injections on day 4, 8 and 12 didn't improve outcomes and had detrimental effects. A single injection after wounding worked best. The results were, control wounds: hairless scars; treated wounds: substantial hair growth by 30 days and indistinguishable from normal skin by 90 days.
  • The drug prescribed to patients is Visudyne. It is a 20 year old drug approved for the treatment of age-related macular degeneration and pathologic myopia. It is used as a photosensitizer for photodynamic therapy to eliminate the abnormal blood vessels in the eye and it is injected intravenously for this use case. Each box contains a glass vial with 15 mg of Verteporfin powder and costs around 1000 USD. Usage: It is reconstituted by injecting 7mL of sterile water into the glass vial to provide 7.5mL of 2 mg/mL Verteporfin. The volume of reconstituted Verteporfin required to achieve 6 mg/m2 body surface area, around 5mL for an adult by Mosteller formula, is withdrawn from the vial and diluted with 5% Dextrose for Injection to a total infusion volume of 30 mL. It is administered intravenously over 10 minutes at a rate of 3 mL/minute. The second step is the light activation of Visudyne using a laser at 15 minutes after the start of the infusion, but this part is irrelevant for wound healing.
    • Note that the dosage used on mice was minuscule in comparison at 30μL of 1 mg/mL Verteporfin, or 0.03mg of Verteporfin, and that it was injected in the skin instead.
  • All patents on Verteporfin have expired, making it possible for anyone to manufacture it. There are manufacturers selling >99% purity Verteporfin at better prices for research purposes, but they don't sell to patients.
  • There is previous work [4] on the role that tension plays during wound healing on humans: "embrace® Active Scar Defense is the only FDA-Cleared scar therapy system designed to relieve tension around incisions, general cuts and lacerations to prevent the formation of new, visible, raised scars before they start."
    • Presumably, completely blocking mechanotransduction at the cellular level using a drug like Verteporfin would work much better.

[1] https://science.sciencemag.org/content/372/6540/eaba2374
[2] https://www.nytimes.com/2021/04/22/health/surgery-scar.html
[3] https://science.sciencemag.org/content/sci/suppl/2021/04/21/372.6540.eaba2374.DC1/aba2374_Mascharak_SM.pdf
[4] https://www.embracescartherapy.com/citations-and-patents

Edited by toagi
Better formatting. Typos.
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  • toagi changed the title to FDA approved drug Verteporfin found to fully regenerate skin, including hair follicles
  • 3 weeks later...
On 5/23/2021 at 10:58 AM, toagi said:

the surgeons made an incision as wide as a thumb and five inches long. When they sutured the cut and injected Verteporfin around the edge, there was dramatically less scarring.

 

This sounds like it could make FUT come back in style. What would be really interesting is to try cutting out some wide existing FUT scars and suturing them back together and injecting this.

 

Edited by BeHappy
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