We will discuss the main reasons why there has been no progress in the treatment of Androgenetic Alopecia for decades. First, we will outline the basic positions, which catch the eye immediately.
1. The effect of finasteride on bald scalp gene expression is not well understood.
2. Potential medications are mostly tested in animals that do not have alopecia.
3. There is not even a hint of hope that we will soon see a cure.
Let us look at the situation and talk about the main results that have been received. Along the way, we will ask a series of rhetorical questions in the hope that there will be people who have the answers.
None of the existing treatment does not convert vellus hair to terminal[1]. In many articles ( with the exception of a few cases, but more on that later) is constantly speculating on this topic, usually shown by the results before and after, and it, of course, says that the number of terminal hairs has increased, but the whole point in the fact that these drugs transferred the terminal hair, which is in telogen stage, into catagen stage. That is, the effect on hair is minimal. This is why minoxidil and finasteride are not helpful for completely bald people. Effective Androgenetic Alopecia treatment is not about accelerating hair growth, but converting vellus hair into terminal hair. The most important thing is that hair follicles do not disappear and under very specific conditions such regeneration was observed [1,2,3].
A very interesting article about prostaglandins level[5]. It says that the level of prostaglandins in the balding area is elevated. Surprisingly, such an important discovery has not been taken apart. There are four important and simple questions that I have not found answers to.
If the phenomenon is repeated, then we will receive an answer to the most important question: are only androgens to blame for baldness, and is there some other enzyme behind the screen, which together with androgens, leads to the development of Androgenetic Alopecia? If, in some case, the transplanted hair vellus into mice skin retains its characteristics and is not transformed into terminal, then we will obtain a qualitative model for the study of Androgenetic Alopecia with human hair, and not with mice hair, which does not always successfully reproduce the properties of balding human hair. After all, as a rule, mice are depilated, then they are given medication and hair growth is compared with the control group, I agree, the results sometimes look impressive, but they do not carry any therapeutic meaning, since these animals do not have alopecia, and this is a very serious simplification. Unsurprisingly, all of the drugs that tested positive in such studies had no apparent effect in real-life clinical trials. Therefore, it is logical to propose the use of transgenic mice in further studies, for example, a mice with an increased expression of the androgen receptor[10] or COX- 2 in the skin. These mice have alopecia, which closely resembles androgenetic alopecia. By the way, I would like to know if minoxidil and finasteride affect hair growth in such special mice.
Conclusion
To put it short, the first thing you must know is the effect of finasteride on gene expression at Androgenetic Alopecia, if he returns it to normal. Then, to obtain an adequate animal model with transplanted human hair, which will correspond to the pathogenesis of Androgenetic Alopecia, and investigate promising drugs only within the framework of such a model. And most importantly, to study the phenomenon of hair transplanted on the skin of a nude mice to the smallest detail, I repeat that this is the first time when hair vellus becomes terminal. I must point out that there are tons of articles on potential treatments for Androgenetic Alopecia, from stem cell transplant to cloning hair on the back of mice. Firstly, I strongly doubt that such methods will be effective in the foreseeable future. Secondly, why reinvent the wheel if hair follicles don't disappear, it's easier find a way to stimulate their growth. I understand that I do not have the medical qualifications to judge so strictly about the current prospects in the treatment of Androgenetic Alopecia, but still I am very disappointed that there are obvious omissions that have not been paid due attention. Unfortunately, the lack of answers to the above questions blocks any discussion of the causes of Androgenetic Alopecia and the creation of a clear strategy for further research to develop a working drug. For a start it is necessary to find unsafe cure remedy for baldness human hair loss, tested on qualitative animal model, and then have to think, how to make it safe.
Decades of waiting for treatment and all in vain. I appeal to people who suffer from baldness, maybe we will change the strategy and stop waiting for a miracle, let's figure out a way to directly offer and order research on specific topics of interest to us, above I described only a small part of what is unknown. Although I may be wrong in some places and I will be glad if someone corrects me.
1. D. Hugh Rushton Michael J. Norris Dominique Van Neste Hair regrowth in male and female pattern hair loss does not involve the conversion of vellus hair to terminal hair
2. Luis A. Garza, Chao-Chun Yang, Tailun Zhao, Hanz B. Blatt, Michelle Lee, Helen He, David C. Stanton, Lee Carrasco, Jeffrey H. Spiegel, John W. Tobias, and George Cotsarelis1 Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells
3. William R Baldness reversed by chemotherapy
4. Helena Collgros , Joaquin Sola Ortigo sa , Maribel Iglesias-Sancho Topical Diclofenac 3% Gel for Actinic Keratosis May Induce Terminal Hair in Male Androgenetic Alopecia: A Report of Three Cases
5. D A Fenton, J S English, and J D Wilkinson Reversal of male-pattern baldness, hypertrichosis, and accelerated hair and nail growth in patients receiving benoxaprofen.
6. Luis A. Garza, Yaping Liu, Zaixin Yang, Brinda Alagesan , John A. Lawson, Scott M. Norberg , Dorothy E. Loy, Tailun Zhao, Hanz B. Blatt, David C. Stanton, Lee Carrasco, Gurpreet Ahluwalia, Susan M Fischer, Garret A. FitzGerald, and George Cotsarelis Prostaglandin D2 Inhibits Hair Growth and Is Elevated in Bald Scalp of Men with Androgenetic Alopecia
7. David K. Bol , R. Bruce Rowley, Ching-Ping Ho, Brigette Pilz , Janet Dell, Mavis Swerdel , Kaoru Kiguchi , Stephanie Muga , Russell Klein and Susan M. Fischer Cyclooxygenase-2 Overexpression in the Skin of Transgenic Mice Results in Suppression of Tumor Development
8. Krajcik RA1, Vogelman JH, Malloy VL, Orentreich N Transplants from balding and hairy androgenetic alopecia scalp regrow hair comparably well on immunodeficient mice.
9. Joanna Bukowska, Marta Kopcewicz, Katarzyna Walendzik, and Barbara Gawronska-Kozak Foxn1 in Skin Development, Homeostasis and Wound Healing
10. Judy S. Crabtree, Edward J. Kilbourne, Bryan J. Peano, Susan Chippari, Thomas Kenney, Christopher McNally, Wei Wang, Heather A. Harris, Richard C. Winneker, Sunil Nagpal A Mouse Model of Androgenetic Alopecia
1. The effect of finasteride on bald scalp gene expression is not well understood.
2. Potential medications are mostly tested in animals that do not have alopecia.
3. There is not even a hint of hope that we will soon see a cure.
Let us look at the situation and talk about the main results that have been received. Along the way, we will ask a series of rhetorical questions in the hope that there will be people who have the answers.
None of the existing treatment does not convert vellus hair to terminal[1]. In many articles ( with the exception of a few cases, but more on that later) is constantly speculating on this topic, usually shown by the results before and after, and it, of course, says that the number of terminal hairs has increased, but the whole point in the fact that these drugs transferred the terminal hair, which is in telogen stage, into catagen stage. That is, the effect on hair is minimal. This is why minoxidil and finasteride are not helpful for completely bald people. Effective Androgenetic Alopecia treatment is not about accelerating hair growth, but converting vellus hair into terminal hair. The most important thing is that hair follicles do not disappear and under very specific conditions such regeneration was observed [1,2,3].
A very interesting article about prostaglandins level[5]. It says that the level of prostaglandins in the balding area is elevated. Surprisingly, such an important discovery has not been taken apart. There are four important and simple questions that I have not found answers to.
- In [6] it is said that transgenic mice expressing COX- 2 in skin develops alopecia. Earlier it was stated that if such mice were given a COX-2 inhibitor after birth, then alopecia does not occur. After receiving celecoxib hair cover continued for several months, but some hair loss had already started. Will hair growth be reversed in animals that have already fully developed alopecia if given a COX- 2 inhibitor?
- We know that the level of PGD2 is elevated in the scalp in androgenetic alopecia. It is necessary to separately consider the balding scalp (there is miniaturized hair) and bald scalp (no visible hair), is there a difference in the level of expression of COX- 2 and PGD2(or other known hair growth inhibitors)?
- The study involved people who did not take finasterid or minoxidil, it’s just waste. After all, I would like to know whether finasteride or minoxidil affects COX-2 and PGD2 levels? By the way, the same applies not only to PGD2, but other hair growth inhibitors such as DKK -1, SFRP -1, SFRP -2, TGF - BETA. If finasteride reduces their expression, it can be concluded that any treatment, based on the manipulation of prostaglandins or other known hair growth inhibitors, will be at least no more effective than finasteride. If finasteride does not significantly affect their expression, then this is a completely different story.
- To check it is necessary artificially increase the level of testosterone in the blood of a nude mice before and after transplanting human hair vellus. This mechanism has been worked out in other studies. Will the above phenomenon be repeated?
- To test, you need to transplant hair vellus into the skin of normal and transgenic mice, which were mentioned earlier. I guess there are a lot of possibilities to solve the problem with the immune system of mice that rejected the transplanted hair, for example, at the same time to give these mice with immunosuppressant. And again to check whether the phenomenon will be repeated with the growth of a new terminal hair instead of vellus hair?
- If you transplant not hair separately, but a small patch of skin from a balding or completely bald scalp into nude mice, will terminal hair grow on this patch of skin?
If the phenomenon is repeated, then we will receive an answer to the most important question: are only androgens to blame for baldness, and is there some other enzyme behind the screen, which together with androgens, leads to the development of Androgenetic Alopecia? If, in some case, the transplanted hair vellus into mice skin retains its characteristics and is not transformed into terminal, then we will obtain a qualitative model for the study of Androgenetic Alopecia with human hair, and not with mice hair, which does not always successfully reproduce the properties of balding human hair. After all, as a rule, mice are depilated, then they are given medication and hair growth is compared with the control group, I agree, the results sometimes look impressive, but they do not carry any therapeutic meaning, since these animals do not have alopecia, and this is a very serious simplification. Unsurprisingly, all of the drugs that tested positive in such studies had no apparent effect in real-life clinical trials. Therefore, it is logical to propose the use of transgenic mice in further studies, for example, a mice with an increased expression of the androgen receptor[10] or COX- 2 in the skin. These mice have alopecia, which closely resembles androgenetic alopecia. By the way, I would like to know if minoxidil and finasteride affect hair growth in such special mice.
Conclusion
To put it short, the first thing you must know is the effect of finasteride on gene expression at Androgenetic Alopecia, if he returns it to normal. Then, to obtain an adequate animal model with transplanted human hair, which will correspond to the pathogenesis of Androgenetic Alopecia, and investigate promising drugs only within the framework of such a model. And most importantly, to study the phenomenon of hair transplanted on the skin of a nude mice to the smallest detail, I repeat that this is the first time when hair vellus becomes terminal. I must point out that there are tons of articles on potential treatments for Androgenetic Alopecia, from stem cell transplant to cloning hair on the back of mice. Firstly, I strongly doubt that such methods will be effective in the foreseeable future. Secondly, why reinvent the wheel if hair follicles don't disappear, it's easier find a way to stimulate their growth. I understand that I do not have the medical qualifications to judge so strictly about the current prospects in the treatment of Androgenetic Alopecia, but still I am very disappointed that there are obvious omissions that have not been paid due attention. Unfortunately, the lack of answers to the above questions blocks any discussion of the causes of Androgenetic Alopecia and the creation of a clear strategy for further research to develop a working drug. For a start it is necessary to find unsafe cure remedy for baldness human hair loss, tested on qualitative animal model, and then have to think, how to make it safe.
Decades of waiting for treatment and all in vain. I appeal to people who suffer from baldness, maybe we will change the strategy and stop waiting for a miracle, let's figure out a way to directly offer and order research on specific topics of interest to us, above I described only a small part of what is unknown. Although I may be wrong in some places and I will be glad if someone corrects me.
1. D. Hugh Rushton Michael J. Norris Dominique Van Neste Hair regrowth in male and female pattern hair loss does not involve the conversion of vellus hair to terminal hair
2. Luis A. Garza, Chao-Chun Yang, Tailun Zhao, Hanz B. Blatt, Michelle Lee, Helen He, David C. Stanton, Lee Carrasco, Jeffrey H. Spiegel, John W. Tobias, and George Cotsarelis1 Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells
3. William R Baldness reversed by chemotherapy
4. Helena Collgros , Joaquin Sola Ortigo sa , Maribel Iglesias-Sancho Topical Diclofenac 3% Gel for Actinic Keratosis May Induce Terminal Hair in Male Androgenetic Alopecia: A Report of Three Cases
5. D A Fenton, J S English, and J D Wilkinson Reversal of male-pattern baldness, hypertrichosis, and accelerated hair and nail growth in patients receiving benoxaprofen.
6. Luis A. Garza, Yaping Liu, Zaixin Yang, Brinda Alagesan , John A. Lawson, Scott M. Norberg , Dorothy E. Loy, Tailun Zhao, Hanz B. Blatt, David C. Stanton, Lee Carrasco, Gurpreet Ahluwalia, Susan M Fischer, Garret A. FitzGerald, and George Cotsarelis Prostaglandin D2 Inhibits Hair Growth and Is Elevated in Bald Scalp of Men with Androgenetic Alopecia
7. David K. Bol , R. Bruce Rowley, Ching-Ping Ho, Brigette Pilz , Janet Dell, Mavis Swerdel , Kaoru Kiguchi , Stephanie Muga , Russell Klein and Susan M. Fischer Cyclooxygenase-2 Overexpression in the Skin of Transgenic Mice Results in Suppression of Tumor Development
8. Krajcik RA1, Vogelman JH, Malloy VL, Orentreich N Transplants from balding and hairy androgenetic alopecia scalp regrow hair comparably well on immunodeficient mice.
9. Joanna Bukowska, Marta Kopcewicz, Katarzyna Walendzik, and Barbara Gawronska-Kozak Foxn1 in Skin Development, Homeostasis and Wound Healing
10. Judy S. Crabtree, Edward J. Kilbourne, Bryan J. Peano, Susan Chippari, Thomas Kenney, Christopher McNally, Wei Wang, Heather A. Harris, Richard C. Winneker, Sunil Nagpal A Mouse Model of Androgenetic Alopecia