new hair growth patent, tyrosone kinease inhibitor....

[michael barry]

http://www.wipo.int/pctdb/en/wo.jsp?WO= ... LAY=CLAIMS


I have zero idea on whether or not there is any validity to this, but chanced upon it. It might be a roundabout way to inhibit epidermal growth factor or whatnot.



I have noticed that the pathways involving hairgrowth keep coming up over and over like beta-catenin, wnt, sonic hedgehog, various prostalgandins etc. Its narrowing the search for the researchers surely enough.....
Them getting to watch neo-natal-like hair follicle development with the follica testing in rodents might be able to further elucidate what happens that marks hairs for later on (or not). It sure as hell cant hurt. It seems like one of the soy isoflavones has a relationship with tyrosone kinease from a brief skim of things......................

 

[docj077]

Well, I've never seen any evidence that patients with gastrointestinal stromal tumors or chronic myelogenous leukemia receiving Gleevec regrow their hair lost through male pattern baldness. However, I don't know if it has ever been studied, either.

 

[harold]

Seems to be centred around the destruction/inactivation of mast cells.

Then, liberation by activated mast cells of mediators (TNF-a, leucotrienes, prostaglandines etc...) can induce inflammation around follicles leading to apoptosis of cells in the germinative matrix. This support that the inflammatory process mediated by mast cells is, at least in part, responsible for the development of alopecia. Local therapeutic strategies aiming at blocking the activation and the survival of mast cells, for instance through inhibition of c-kit or c-kit signaling can thus be beneficial and could help to decrease hair-loss in such condition.

More specifically, the present invention proposes to use c-kit specific kinase inhibitors to inhibit mast cell proliferation, survival and activation. A new route for promoting hair growth, preventing or minimizing hair loss is provided, which consists of destroying mast cells playing a role in the apoptosis of cells in the hair follicles. It has been found that tyrosine kinase inhibitors and more particularly c-kit inhibitors are especially suited to reach this goal.

Am in a real undecided stage about what to do/what factors are more important in male pattern baldness - inflammation and regeneration. Have been toying with the idea of using topical glucocorticoids. However glucocorticoids have the potential to be strongly antiproliferative. If used at enough potency/duration that they lead to the much feared skin atrophy then they can be associated with hair thinning etc. It seems to be pretty much impossible to use current glucocorticoids without some (not detectable through human investigation but through ultrasound) skin atrophy. Then again they are a cheap, relatively obtainable, powerful immunosupressant. And their use has been associated with hypertrichosis and they are used to treat aopecia areata. Though of course AA is a totally immune mediated disease.
Then again some of the evidence from the Cotsarelis PGD2 patent and other sites almost makes male pattern baldness look like an organ rejection condition (the hair follicle is a miniature organ effectively). CD200 was downregulated in follicles from balding areas. Along with an upregulation of MHC1 and MHC2 markers on these follicles it seems that they are marked as potential dangers for the immune system.

J Invest Dermatol. 2004 Nov;123(5):880-7.Click here to read Links
Expression of CD200 on epithelial cells of the murine hair follicle: a role in tissue-specific immune tolerance?
Rosenblum MD, Olasz EB, Yancey KB, Woodliff JE, Lazarova Z, Gerber KA, Truitt RL.

Department of Pediatrics, Medical College of Wisonsin, Milwaukee, Wisconsin, USA.

CD200 (OX-2) is a transmembrane glycoprotein that transmits an immunoregulatory signal through the CD200 receptor (CD200R) to attenuate inflammatory reactions and promote immune tolerance. CD200 expression in the skin has not been described previously. We now report that freshly isolated cells of the murine epidermis contain a subpopulation of major histocompatibility complex (MHC) class II-negative, CD3-negative keratinocytes that are CD200-positive. CD200 expression was accentuated in keratinocytes comprising the outer root sheath of the murine hair follicle (HF). When syngeneic skin grafts were exchanged between gender-matched wild-type (WT) and CD200-deficient C57BL/6 mice, significant perifollicular and intrafollicular inflammation was observed, eventually leading to the destruction of virtually all HF (alopecia) without significant loss of the CD200-negative grafts. Minimal and transient inflammation was observed in WT grafts, which persisted long term with hair. There was a 2-fold increase in graft-infiltrating T cells in CD200-deficient skin at 14 d. Alopecia and skin lesions were induced in CD200-deficient hosts by adoptive transfer of splenocytes from WT mice previously grafted with CD200-negative skin, but not from mice grafted with WT skin. Collectively, these results suggest that the expression of CD200 in follicular epithelium attenuates inflammatory reactions and may play a role in maintaining immune tolerance to HF-associated autoantigens.

Am beginning to think that something stronger is needed than what i have been using on the local immune-modulating front. But that whole antiproliferative thing gives one pause. In AA it seems that the ratio of immune to antiproliferative fators behind the disease is high enough that even very strong local and sytemic regimens can be very beneficial. I am not so sure this is the case in male pattern baldness. If a definitive chain of events or link between the two could be established we might have a better idea or a better clue at least.
Just some random thoughts....
hh

 

[harold]

Hmmmmm. I have always thought of the main factor which distinguishes male pattern baldness/Androgenetic Alopecia from other forms of hair loss (which may be far more dramatic) was the miniaturization of follicles. And I had believed that this was more or less unique to Androgenetic Alopecia. The fact that BMPs are negative regulators of hair follicle size and antagonistic of wnt signalling therefore makes them of interest and possibly makes that route more interesting than the inflammatory one. The only case I have seen of an immuno-modulatory agent doing that was topical tacrolimus was said to increase the size of follicles in mice.

However this article does mention that hair miniaturization is a feature of AA. Perhaps the process is just so much more rapid typically that thin/miniaturized/vellus hairs are rarely scene as the follicle progresses towards the non-functioning stage so much quicker than it does in Androgenetic Alopecia. Maybe Androgenetic Alopecia is more or less a patterned (AA hair can be lost from any part of the scalp), slower progressing form of AA? Probably not. But I am going to look around a little more and see if its totally out of the question.

Arch Dermatol. 2003 Dec;139(12):1555-9.Click here to read Links
Histopathologic features of alopecia areata: a new look.
Whiting DA.

Baylor Hair Research and Treatment Center, Dallas, TX 75246, USA. daddoc@dallasassocderm@com

BACKGROUND: A peribulbar lymphocytic infiltrate is the expected histologic feature of alopecia areata, but it is absent in many scalp biopsy specimens. Other diagnostic criteria are needed. OBJECTIVE: To establish the histologic features of alopecia areata in scalp biopsy specimens taken from different types of alopecia areata, using follicular counts to relate biopsy findings to stages of the disease. METHODS: Fifty consecutive new patients with alopecia areata were studied. Four-millimeter punch biopsy specimens were taken from the scalp in areas of recent, active hair loss; old, inactive hair loss; or recent hair regrowth. Specimens were sectioned horizontally. Terminal and vellus-like hairs were counted. Inflammation and fibrosis around lower and upper follicles were rated. RESULTS: The histopathologic features of alopecia areata were not significantly affected by the sex, age, and race of the patient or by the type, percentage of hair loss, total duration, or regression of alopecia areata. The major factor affecting the histopathologic features was the duration of the current episode of alopecia areata. In the acute stage, bulbar lymphocytes surrounded terminal hairs in early episodes and miniaturized hairs in repeated episodes. In the subacute stage, decreased anagen and increased catagen and telogen hairs were characteristic. In the chronic stage, decreased terminal and increased miniaturized hairs were found, with variable inflammation. During recovery, increasing numbers of terminal anagen hairs from regrowth of miniaturized hairs and a lack of inflammation were noted. CONCLUSIONS: The histopathologic features of alopecia areata depend on the stage of the current episode. Alopecia areata should be suspected when high percentages of telogen hairs or miniaturized hairs are present, even in the absence of a peribulbar lymphocytic infiltrate.

 

[docj077]

I don't think we can use these. Prolonged use or higher doses cause dilated cardiomyopathy.

Tyrosine kinases exist all over the body. This wouldn't work.