"Wonder pill" to cure MPB in 5 years.

[JDW]

This recent patent suggests that this class of drugs work on MPB too...

Here is the link:
http://www.google.com/patents/WO2014013014A1?cl=en

So this is potentially very promising

[BoSox]

This recent patent suggests that this class of drugs work on MPB too...

Here is the link:
http://www.google.com/patents/WO2014013014A1?cl=en

Can somebody sum this up, what exactly does it mean?

[hgs1989]

This recent patent suggests that this class of drugs work on MPB too...

Here is the link:
http://www.google.com/patents/WO2014013014A1?cl=en

if the pill works as in the patent (a stem cell activator) it will definitely work for MPB. remember Cotsarelis said that balding scalp has as much stem cells as non balding one. something is stopping the activation of those stem cells in a balding scalp. he suspected PGD2 but that is another subject. in summary, if this jak inhibitor works as the patent says ; an epidermal stem cell activator; then we have a potential treatment if not a cure.

[whatsgoingon]

posting to see updates on this thread.

[hgs1989]

looks like it will be a male pattern baldness treatment. check this patent out by Dr. christiano: https://www.google.com/patents/WO201...ed=0CB0Q6AEwAA

the important part is" The JAK-STAT signaling pathway has been implicated in several developmental processes, and most recently in stem cell maintenance, activation and differentiation. In the course of the inventor's topical treatment studies using JAK3 in the C3H/HeJ AA mouse model, it was noticed that the hairs that regrew did so with two striking features that were different from systemic administration: 1) hair regrowth was very rapid; and 2) the hair coat was darkly pigmented. Without being hound by theory, in addition to the JAK3 inhibitor eliminating pathogenic T cells from the skin, the JAK3 inhibitor also has a direct effect on the hair follicle itself, for example, via an anagen-promoting effect,

[80328] The dynamics of the JAK-STAT signaling pathway were first interrogated using a targeted RT-PCR array containing readouts of JAK-STAT signaling (FIG. 32), and compared gene expression between the telogen vs. anagen stages of the normal hair cycle (FIGS. 32-35).

[80329] This data revealed that many components of JAK-STAT signaling were upregulated in telogen and downregulated in anagen phase of the normal hair cycle, indicating that in the context of the hair cycle, JAK-STAT signaling can be associated with maintaining stem cell quiescence in telogen (FIG. 35).

[80330] To test whether inhibition of JAK-STAT signaling could therefore trigger the telogen-to-anagen transition, a topical JAK3 inhibitor was applied to test whether anagen could be induced in normal mouse skin in telogen.

[80331] Indeed, topical administration of a JAK3 inhibitor resulted in a striking anagen induction in mouse skin in telogen, compared to vehicle alone. This was associated with marked proliferation of keratinocyte matrix cells, and the induction and growth of robust pigmented anagen hairs after 1-2 weeks {see FIGS. 38-43 ).

[80332] This observation was compared to a positive control SAG (sonic hedgehog agonist) which is known to have the same effect, and the JAK3 inhibitor was comparable in its effect on anagen induction (FIGS. 38, 42, 43).

[80333] Without being bound by theory, these findings indicate that blockade of JAK- STAT signaling in telogen mimics in part the molecular events of anagen initiation, and can be a useful therapeutic agent for hair growth, using topical JAK inhibitors to induce telogen hairs to re-enter anagen."

points taken are :
1- the jak inhibitor has a direct effect on the hair follicle. besides suppressing the immune system.
2- JAK up regulation is somehow responsible for the inactivation of follicle stem cells.
3- JAK inhibition had a comparable effect of anagen induction as a sonic hedge hog agonist.
4- the JAK inhibitor can be delivered topically.
5- points 1 to 4 are for normal skin mice. not Alopecia areata mice.

[sdsurfin]

looks like it will be a male pattern baldness treatment. check this patent out by Dr. christiano: https://www.google.com/patents/WO201...ed=0CB0Q6AEwAA

the important part is" The JAK-STAT signaling pathway has been implicated in several developmental processes, and most recently in stem cell maintenance, activation and differentiation. In the course of the inventor's topical treatment studies using JAK3 in the C3H/HeJ AA mouse model, it was noticed that the hairs that regrew did so with two striking features that were different from systemic administration: 1) hair regrowth was very rapid; and 2) the hair coat was darkly pigmented. Without being hound by theory, in addition to the JAK3 inhibitor eliminating pathogenic T cells from the skin, the JAK3 inhibitor also has a direct effect on the hair follicle itself, for example, via an anagen-promoting effect,

[80328] The dynamics of the JAK-STAT signaling pathway were first interrogated using a targeted RT-PCR array containing readouts of JAK-STAT signaling (FIG. 32), and compared gene expression between the telogen vs. anagen stages of the normal hair cycle (FIGS. 32-35).

[80329] This data revealed that many components of JAK-STAT signaling were upregulated in telogen and downregulated in anagen phase of the normal hair cycle, indicating that in the context of the hair cycle, JAK-STAT signaling can be associated with maintaining stem cell quiescence in telogen (FIG. 35).

[80330] To test whether inhibition of JAK-STAT signaling could therefore trigger the telogen-to-anagen transition, a topical JAK3 inhibitor was applied to test whether anagen could be induced in normal mouse skin in telogen.

[80331] Indeed, topical administration of a JAK3 inhibitor resulted in a striking anagen induction in mouse skin in telogen, compared to vehicle alone. This was associated with marked proliferation of keratinocyte matrix cells, and the induction and growth of robust pigmented anagen hairs after 1-2 weeks {see FIGS. 38-43 ).

[80332] This observation was compared to a positive control SAG (sonic hedgehog agonist) which is known to have the same effect, and the JAK3 inhibitor was comparable in its effect on anagen induction (FIGS. 38, 42, 43).

[80333] Without being bound by theory, these findings indicate that blockade of JAK- STAT signaling in telogen mimics in part the molecular events of anagen initiation, and can be a useful therapeutic agent for hair growth, using topical JAK inhibitors to induce telogen hairs to re-enter anagen."

points taken are :
1- the jak inhibitor has a direct effect on the hair follicle. besides suppressing the immune system.
2- JAK up regulation is somehow responsible for the inactivation of follicle stem cells.
3- JAK inhibition had a comparable effect of anagen induction as a sonic hedge hog agonist.
4- the JAK inhibitor can be delivered topically.
5- points 1 to 4 are for normal skin mice. not Alopecia areata mice.

That does sound promising, although I feel like the treatments for MPB will come up against more issues than with AA. I think there simply HAS to be a whole set of links between the two diseases- there's no way the body kills off follicles in totally different ways, even if the triggers are the same. Also, it seems evident that there is an immunological and inflammatory process associated with MPB. It would be exciting if a topical immune therapy could be combined with an anti androgen. That might be the future of treatments before hair regeneration with stem cells happens. The members of this forum should email Christiano and ask if there are implications in all this for MPB. Hopefully some researchers are tying this all together.

[sdsurfin]

That Christiano patent is pretty fascinating if you read all of it. Goes into DP culturing and gene therapy. I think that Alopecia areata is probably going to be a thing of the past very soon, it seems like they have the mechanisms for it pretty figured out. MPB is more complex, but I hope that there are shared characteristics. Christiano is a beast, if only there were a man that was as passionate and dedicated as her to the pursuit if curing MPB. It's interesting that she published this patent a year ago, just goes to show that they had this Areata treatment figured out a while ago, and whatever they are working on right now could be way more advanced. Here's an interesting snipped from the patent:

Various routes of administration and various sites of cell implantation can be utilized, such as, subcutaneous or intramuscular, in order to introduce the aggregated population of cells into a site of preference. Once implanted in a subject (such as a mouse, rat, or human), the aggregated ceils can then stimulate the formation of a hair follicle and the subsequent growth of a hair structure at the site of introduction. In another embodiment, transfected cells (for example, cells expressing a protein encoded by a Jak3 gene are implanted in a subject to promote the formation of hair follicles within the subject. In further embodiments, the transfected cells are cells derived from the end bulb of a hair follicle (such as dermal papilla cells or dermal sheath cells). Aggregated cells (for example, cells grown in a hanging drop culture) or transfected cells (for example, cells produced as described herein) maintained for 1 or more passages can be introduced (or implanted) into a subject (such as a rat, mouse, dog, cat, human, and the like).

[80228] Subcutaneous administration can refer to administration just beneath the skin (i.e., beneath the dermis). Generally, the subcutaneous tissue is a layer of fat and connective tissue that houses larger blood vessels and nerves. The size of this layer varies throughout the body and from person to person. The interface between the subcutaneous and muscle layers can be encompassed by subcutaneous admins stration,

[00229] This mode of administration can be feasible where the subcutaneous layer is sufficiently thin so that the factors present in the compositions can migrate or diffuse from the locus of administration and contact the hair follicle cells responsible for hair formation. Thus, where intradermai administration is utilized, the bolus of composition administered is localized proximate to the subcutaneous layer.

[8(5230] Administration of the cell aggregates (such as DP or DS aggregates) is not restricted to a single route, but can encompass administration by multiple routes. For instance, exemplary administrations by multiple routes include, among others, a combination of intradermal and intramuscular administration, or intradermal and subcutaneous administration. Multiple administrations can be sequential or concurrent. Other modes of application by multiple routes will be apparent to the skilled artisan.

[80231] in other embodiments, this implantation method will be a one-time treatment for some subjects. In further embodiments of the invention, multiple cell therapy implantations will be required. In some embodiments, the cells used for implantation will generally be subject-specific genetically engineered cells. In another embodiment, ceils obtained from a different species or another individual of the same species can be used. Thus, using such cells can require administering an immunosuppressant to prevent rejection of the implanted cells. Such methods have also been described in United Staies Patent No. 7,419,661 and PCT application publication WO 2001 /32840, and are hereby incorporated by reference. [8(5232] In one embodiment, an inhibitor or agonist of the invention can be incorporated into pharmaceutical compositions suitable for administration, for example the inhibitor and a pharmaceutically acceptable carrier.

[hgs1989]

That Christiano patent is pretty fascinating if you read all of it. Goes into DP culturing and gene therapy. I think that Alopecia areata is probably going to be a thing of the past very soon, it seems like they have the mechanisms for it pretty figured out. MPB is more complex, but I hope that there are shared characteristics. Christiano is a beast, if only there were a man that was as passionate and dedicated as her to the pursuit if curing MPB. It's interesting that she published this patent a year ago, just goes to show that they had this Areata treatment figured out a while ago, and whatever they are working on right now could be way more advanced. Here's an interesting snipped from the patent:

Various routes of administration and various sites of cell implantation can be utilized, such as, subcutaneous or intramuscular, in order to introduce the aggregated population of cells into a site of preference. Once implanted in a subject (such as a mouse, rat, or human), the aggregated ceils can then stimulate the formation of a hair follicle and the subsequent growth of a hair structure at the site of introduction. In another embodiment, transfected cells (for example, cells expressing a protein encoded by a Jak3 gene are implanted in a subject to promote the formation of hair follicles within the subject. In further embodiments, the transfected cells are cells derived from the end bulb of a hair follicle (such as dermal papilla cells or dermal sheath cells). Aggregated cells (for example, cells grown in a hanging drop culture) or transfected cells (for example, cells produced as described herein) maintained for 1 or more passages can be introduced (or implanted) into a subject (such as a rat, mouse, dog, cat, human, and the like).

[80228] Subcutaneous administration can refer to administration just beneath the skin (i.e., beneath the dermis). Generally, the subcutaneous tissue is a layer of fat and connective tissue that houses larger blood vessels and nerves. The size of this layer varies throughout the body and from person to person. The interface between the subcutaneous and muscle layers can be encompassed by subcutaneous admins stration,

[00229] This mode of administration can be feasible where the subcutaneous layer is sufficiently thin so that the factors present in the compositions can migrate or diffuse from the locus of administration and contact the hair follicle cells responsible for hair formation. Thus, where intradermai administration is utilized, the bolus of composition administered is localized proximate to the subcutaneous layer.

[8(5230] Administration of the cell aggregates (such as DP or DS aggregates) is not restricted to a single route, but can encompass administration by multiple routes. For instance, exemplary administrations by multiple routes include, among others, a combination of intradermal and intramuscular administration, or intradermal and subcutaneous administration. Multiple administrations can be sequential or concurrent. Other modes of application by multiple routes will be apparent to the skilled artisan.

[80231] in other embodiments, this implantation method will be a one-time treatment for some subjects. In further embodiments of the invention, multiple cell therapy implantations will be required. In some embodiments, the cells used for implantation will generally be subject-specific genetically engineered cells. In another embodiment, ceils obtained from a different species or another individual of the same species can be used. Thus, using such cells can require administering an immunosuppressant to prevent rejection of the implanted cells. Such methods have also been described in United Staies Patent No. 7,419,661 and PCT application publication WO 2001 /32840, and are hereby incorporated by reference. [8(5232] In one embodiment, an inhibitor or agonist of the invention can be incorporated into pharmaceutical compositions suitable for administration, for example the inhibitor and a pharmaceutically acceptable carrier.

as much as interesting they are, I think it is here just to protect rights to invention. you would see this type of delivery methods in every hair product patent. I doubt it will be anything far from basic oral, topical or injectable treatment.

[sdsurfin]

as much as interesting they are, I think it is here just to protect rights to invention. you would see this type of delivery methods in every hair product patent. I doubt it will be anything far from basic oral, topical or injectable treatment.

I think you missed the whole point. The delivery method doesn't matter. the point is she's talking about reprogramming DP cells with the same protein changes that are being used against Areata, and making DP aggregates to put into balding scalp.

[hgs1989]

I think you missed the whole point. The delivery method doesn't matter. the point is she's talking about reprogramming DP cells with the same protein changes that are being used against Areata, and making DP aggregates to put into balding scalp.

I understand that but I still think that if she is seeking a commercial product regarding JAK inhibition it would be via oral , topical or injections. maybe she is working on reprogramming DP cells (since she is also involved in culturing DP cells in spheroids) but this is very far from a commercial product and she put here just to cover a potential method and protect her rights to the invention. I could e wrong anyway and that this is her main interest, but I doubt it. this stuff is very complicated and she has already conducted trials on humans. the trials if I am not mistaken were based on oral administration.