MrFox

So I wanted to comment on this post because I feel it has come up multiple times in the discord chat as well as on this forum. There is a lot of speculation around what efficacy this drug will have on existing scars, and there are definitely those that are solely interested in verteporfin for scar revision. I think the only credible information we have at this point is from the lead researcher on the Stanford studies, Dr. Michael Longaker. I am highly skeptical of anybody saying it won't work, because no one has tested it in that capacity! I personally believe the researchers at Stanford have a much better understanding than all of us on the underlying mechanisms involved, and until there is proof to the contrary, I will continue to default to the research and information coming from them. I have posted quotes directly from Dr. Longaker below: Quote from New York Times article: "His imagination soared. He might be able to prevent scars with a few quick injections of verteporfin. And there was no reason to think he couldn’t go even farther. A patient who had a disabling and disfiguring scar could go to a surgeon who could dab the scar with lidocaine to numb the skin, cut open the scar, inject verteporfin around the edges, and close the wound. Would it reheal without the scar?" https://www.nytimes.com/2021/04/22/health/surgery-scar.html Another quote from an interview on radio health journal: "This person lives a long time. Some people have many scars. So this would not only be an injection of Verteporfin when the surgeon is closing the incision at the end of the operation, but now you can say, oh, what about all those other scars that have existed for a long time? So one could imagine lidocaine cream being put on the scar, or injection of lidocaine, come back in about 20 minutes and the surgeon excises the scar under local anesthesia in the office, and then injects Verteporfin and the closure, and then it's closed. So there's many, many, many millions of existing scars that could be revised." https://radiohealthjournal.org/advances-eliminate-scarring/ From Dr. Longaker's quotes, I think it is a reasonable to assume that he believes that excising existing scar tissue and injecting Verteporfin would cause the wound to heal in a similar manner. If we continue to have positive results, I definitely feel that is worth trying to excise a smaller existing scar, such as an FUE scar, and injecting Verteporfin.

I think this is why it is so important to keep pushing testing, because this is really the first attempt at it. We don't even know if this is the optimal dosing yet and we already have had a big improvement over baseline scarring. I don't think we should worry too much about the hairs being thin at this point either, we continue to see big improvements with every update so it may well be this is just the natural process it takes for the hair to grow. Even with current hair transplantation we know the hairs take a while to start growing completely normal again, stands to reason the same would be true for newly created follicles.

I see a little bit of scarring in the test area for the .24 dose but I am having a hard time seeing the scarring in the higher doses. I agree more time is likely to produce more skin remodeling if it is anything like the porcine model. The presence of new hair follicles means the skin is definetley reacting differently at this point.

I would agree, I have seen no evidence that this would only grow hair in one region of the scalp as opposed to another. The research indicates that if it works, it's going to work on any part of the skin, and that the hair that is produced in that specific area is going to follow your genetics. I would think that as long as someone was to remain on a 5alpha-reductase inhibitors (oral or topical) it would inhibit miniaturization of a new hair follicle that was produced via extraction and treated with Verteporfin.

@Melvin- Moderator Thank you for asking my questions, I really appreciate it! And thank you @DrTBarghouthi for partaking in the interview and again for undertaking the study! I think the way I worded my question about the recipient area may have lead to some confusion. I am aware that injecting Verteporfin alone would be insufficient to regenerate the follicles, there would need to be some sort of injury occurring first. I was more referring to the protocol for injuring the tissue. For example we could extract miniaturized follicles via an FUE punch and then inject Verteporfin. Someone correct me if I'm wrong, but I was under the impression that even severally miniaturized hairs are still able to be viewed under a microscope, even if only the follicular opening remains. I would argue that the follicle that would regenerate would be more than likely a hair that is not miniaturized. As we all know DHT takes time to affect the follicle. So in theory as long as someone remained on the DHT blocking drugs, either topical or oral, that hair follicle should not miniaturize. @DrTBarghouthi Would love to hear your thoughts on this!? Thanks again!

If Verteporfin does work to regrow hair, how would he envision it be used in the recipient area? Does he plan to share to his protocol and results with other surgeons and clinics, so this becomes more avaiable to all of us? How could we avoid shortage issues in the future, will it be possible to source the brand name Visudyne?

Great news! Hopefully we will have some solid evidence on wether it works by the end of the year!

Yes but also remember these are temporary side affects, not permanent.

The following is a presentation given by the team at Stanford about the results of their soon to be published study using Verteporfin on Red Duroc Pigs. I will reiterate that this is something that we seriously need more Hair Restoration Surgeons to show an interest in using off-label! I have included pictures from the summary as well as the link to the video presentation, it is the second lecture. In addition to the pig model, she also spoke about similar findings in a Xenograph model using human skin tissue. The drug was well tolerated in the study, which is something we were already aware off with Verteporfin being FDA approved for over 20 years. @Melvin- Moderator is this something you could share again with more doctors when speaking with them!? The summary of the methods used were as follows: "Full-thickness excisional wounds (2x5cm hexagons) were produced on the dorsum of adult pigs. Wounds received intradermal verteporfin (YAP inhibitor; 2mg/mL) or vehicle control (PBS) followed by primary repair with 3-0 Vicryl deep dermal and 3-0 Monocryl running subcuticular sutures. Cutometer measurements were obtained to assess tissue stiffness every two weeks. Wounds and unwounded skin were harvested after 16 weeks for histologic (hematoxylin and eosin staining), mechanical (Instron strength testing), and scRNA-seq (10X Chromium) analyses."

So is this form of hair loss caused by DHT as well? It seems like it is not a very well understood form of hair loss.

We're not even sure if we need the photo activated version of Verteporfin yet, but to my knowledge it was not mentioned in the study by Stanford, suggesting that they did not need to control for it. Additionally they inject a larger amount of Vertporfin directly into the bloodstream when treating macular degeneration, so it very unlikely that it will cause serious toxicity in our bodies. Longaker seems to believe the drug will be used in almost every clinical setting at some point, so clearly it cannot be that difficult to control for otherwise there would have been some mention of it. But even if they do have to control for it, its not like the don't already have protocols in place for it. This drug has been used for over 20 years now, and has very low risk profile in comparison to other drugs. Additionally hair transplant surgeons do have to worry about serious consequence already at their practices, there can be serious complications with hair transplantation. You make it seem like it is a risk free surgery. They already inject medication into people scalps, i.e. numbing agents. You don't think they have to control for that? If the drug works as we believe it does, any surgeon would be at disadvantage to not offer it at their clinic. Patients are not going to want to go to any given provider if they offer a lesser service. Why do you think so many clinics have adopted FUE? It's clearly because of patient demand. Idk about you but I would gladly pay more and go to a different clinic if it meant could avoid having scars.

Completely agree, I think you will have options, which I think is always better for the patient/customer. Also I think this reiterates that the use of this drug is not going to be the end of hair restoration surgery or clinics. I think it actually gives the surgeon and patient more options and better outcomes. Not to mention more people willing to do the procedures. The clinics stand to make at least an equal amount of money and potentially more. I think it is mutually beneficial, so again I'm not quite sure why there isn't more interest here!

Yes, I think you would be correct. Your genetics are not going to change, so you would more than likely have the same hair loss pattern again and again, if you did not prevent it from doing so with drug intervention. For most it is a well tolerated drug, not to mention there other treatments coming available such as topical dutasteride or finasteride as well as other topical AR antagonists which may have less side effects. Perhaps people who had a very slow progression could get away with just gettin a session every few years as well. I think there would be options, and you would be able to decide what is personally best for you.

Again I think there are only two scenarios where this would be a viable option. People who do not want to stay on drugs long term and perhaps someone who is unhappy with their biological hairline. It may be that the hair would only grow back in the same pattern, as it is genetic/hormonal that affects everyone's hairline, even without any hair loss. So if you were born with a hairline you were unhappy with, it may still be necessary to have some transplantation. Otherwise to me transplanting hairs from the donor area to the top or front of the head seems like an unnecessary step if Verteporfin works to regenerate follicles. I don't see why it should work in the donor area exclusively. Miniaturized hairs are still visible under a microscope, even for severely balding patients. Potentially you would extract the miniaturized hair and a new terminal hair would appear. Perhaps with someone with a higher Norwood scale it would take several sessions. I also believe you could also reverse any transplanted hairs through that process. So if you were unhappy with the results you could basically have those follicles extracted as well. I think that the inherent limitation of hair transplantation could also be avoided through the later process. The hair could potentially grow back to normal hair density (different for each patient) which is known to be difficult to achieve in hair transplantation. Additionally each individual hair follicle would be the right color and diameter, which can also be a variable in hair transplantation. You would also not need to worry about the correct hair angle or depth of implantation. I feel like that is just not possible for any surgeon, no matter how talented they are, to be able to reproduce the naturalness of someone's own native hairline. I don't think there is anybody on this forum who would not sign up to have their hairline from when they were 14 or 15! I mean look at that 78 year old burn patient, that hairline looked extremely natural on him from the burn and that was a completely uncontrolled consequence of wound induced hair follicle neogensis.

I know you're joking but I think there is a high possibility it works in the recipient area in that manner! Again hair restoration surgeons/clinics would be the ideal people to carry out that treatment. Their clinics are already set up to handle something like that. Not to mention all the money they would be able to make offering scar repair.

I'm not sure why we are not getting more doctors/clinics to comment on this research. We are not asking them to jump into using the drug without further research being done, it would just be nice to have some sort of dialogue. It has been over a year since the research was published, and we are talking about an already FDA approved drug that could be used off-label immediately. It seems strange to me that none of these top clinics will even make a comment on it, other than they heard about it, and they don't know. We are talking about something that can potentially change the entire industry top to bottom and it seems to me that Hair Surgery Clinics will still be necessary to perform this work with Verteporfin, so it is both in the patients best interest as well as their own. Idk maybe we need to tag some more clinics in this thread....?

Hair follicle neogensis means the development of new follicles. The 78 year old burn patient in the video received full thickness burns. In those regions the hair follicle are completely destroyed. So the hair that was present after the burn healed was not old hair that had been triggered to grow, but completely new follicles that he did not have before the burn. In theory this would be the same protocol for hair removed from the donor area. You are creating a wound and the follicle is gone. By injecting Verteporfin, the wound is inhibited from certain mechanical signals and therefore contracture and fibrosis do not occur. The skin is than pushed into a regenerative state, that creates new follicles, adipocytes, sweat glands, sebaceous glands, blood vessels, etc.

I felt like this video was relevant to this/our discussion @DrTBarghouthi. The case study of the 78 year old man in this video received full thickness burns to his scalp. The total surface area was rather large and he refused any sort surgical intervention. This is an example of hair neogensis and skin regeneration occurring naturally in nature, given the right circumstances. If verteporfin works to elicit this process doesn't it stand to reason that even large wounds, such as from FUT, would be able to reproduce the lost skin? Would be great to hear other's opinions on this as well!!!

Not sure if I tagged the last post properly....

@Melvin- Moderator What did they have to say?

I've been thinking about this as well, but ultimately I think the only way we are going to know is by trying. As far as the scar tissue I think as long as the scar was removed, the drug would behave in a similar fashion to a wounded area without a scar. The mechanism is the same regardless. I don't think your body would lose the capacity to regenerate a wound just because it has been longer. Dr. Longaker has stated that he believes it will work with scars. With regards to miniaturized hair I would argue that a terminal hair unaffected by DHT would be the most likely scenario, as the only reason the follicle is miniaturized is because of long term exposure to DHT. That being said I think it would be likely that hair regrown would be susceptible to miniaturizing again, and therefore drugs such as finasteride would be needed to prevent that. It seems to me that the underlaying mechanism for whether a hair would be terminal or vellus comes to down to the individual genetics. I agree I think if you never had a terminal hair in a certain location it would not suddenly become terminal, so I do not think it would have much usefulness for beard growth.

I couldn't agree more with minimizing risk, especially in the early stages of testing the drug. Wouldn't there need to be some method of injuring the skin in the recipient areas in order for the drug to have an affect?

First I appreciate your responses Dr. Barghouthi. I think the initial testing of the drug would benefit from the process you are describing, minimizing the amount of tissue that needs healing in case the drug does not work as well as we hope. That being said, I don't quite understand the reasoning behind minimizing the amount that needs to be healed if it works as well as it did in the mouse study in humans. This drug as the potential to heal deep full thickness wounds, with large sections of skin. I believe from all of the literature I have read that if Verteporfin brings back fully functional skin tissue than secondary intention will not be an issue, because scar tissue is not forming in the first place. Additionally with all due respect we have no information proving that this will not work on balding areas, that is purely speculative in my opinion. All of the testing as been on mice and pigs, who do not suffer from alopecia. We simply do not know that it won't regrow hair in balding areas if it works in other areas as well. Additionally there are instances of hair neogensis occurring in humans, who suffer from alopecia, we know that it is possible but extremely rare. The article linked below concerns a man who suffered from 3rd degree burns on his head. Any lingering follicles he had would have been destroyed but that deep of a burn, and the man was clearly suffering from alopecia before this burn occurred. He clearly has had at least some follicle neogensis occur. https://www.bmj.com/content/bmj/293/6562/1645.1.full.pdf

Would it be possible to not stitch the two edges together after the scar is excised? In another Stanford porcine study they used a drug similar to Verteporfin but it was incorporated in hydrogel patches which they changed ever other day. Again I realize we are a long way from knowing if the drug will be as affective in humans and will produce the results that are we are hoping it will. If it does work accordingly it seems like the later method would be a more ideal treatment pathway as you would be restoring the original amount of skin that existed before the surgery. https://www.nature.com/articles/s41467-021-25410-z#Sec9 Additionally I've seen a lot of discussion about using this as a conjunction with hair transplantation surgery to prevent scarring. I personally feel like restoring the donor region with scar revision surgeries w/ Verteporfin makes complete sense, but I don't quite see the logic behind using the drug in conjunction with doing a new hair transplant surgery if it works to fully regenerate follicles. It seems most patients are already using drugs such as Dutasteride and Finasteride which blocks the further progression of hair loss, so why not just use Verteporfin in the balding areas and not bother with transplanting follicles? It feels like this would potentially provide the most natural and asthetic results for patients. It would allow for each patients own natural hair patterns and densities to be restored and would take out a lot of inherent risks with transplantation away. I understand that there may be individuals who have bad reactions to the drugs or do not want to continue taking the drug long term, so perhaps transplantation makes sense for those patients. Again I understand this is the early stages and we do not understand all of the variable as of yet.

Obviously there is still a lot of testing that needs to be done to see if the this an effective treatment, and this is more of a theoretical question, but I am curious how this would be applied in the use of FUT scars? For the FUE scars it seems pretty straight forward with removing the small scars with a punch similarly used in the procedure to begin with and ejecting Verteporfin, maybe putting some protective dressing over while it heals. With an FUT scar would the scar be excised and then stitched/stapled together and injected with verteporfin? I don't think that would be the best solution. In theory wouldn't it be better to remove the scar tissue and basically allow the amount of skin tissue that was originally removed to regenerate?