Dr. Angela Christiano - Targeting Immune Cells in Alopecia Areata

hellouser

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[video=youtube;5VUNOijU-Jk]https://www.youtube.com/watch?v=5VUNOijU-Jk[/video]

Update:
Dr. Angela Christiano has done an interview and talks about JAK inhibitors for Androgenetic Alopecia when applied locally in dermal papilla cells, topical concentration (short answer is that it needs to be high), etc. Note, Rapunzel affiliation and progress was NOT inquired about.
https://vimeo.com/149187741
 

Swedishnyc

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JAK for Androgenetic Alopecia

Thank you hellouser for all ur posts.
However Lets get Down to the basic, and Not all This information on how it Works on AA.

You Said she allready know that the topical solution has to be High for Androgenetic Alopecia (male pattern baldness)
So This mean she allready has a topical cream tested and trialed??

Thank you
 

hellouser

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Thank you hellouser for all ur posts.
However Lets get Down to the basic, and Not all This information on how it Works on AA.

You Said she allready know that the topical solution has to be High for Androgenetic Alopecia (male pattern baldness)
So This mean she allready has a topical cream tested and trialed??

Thank you

I believe so, there are patents on the jak inhibitors that mention topical formulations, but we dont know the vehicle or the concentration. But in the interview she mentions a high concentration, so perhaps we need a lot of it.... but the stuff is already WILDLY expensive.

However, if physicians can prescribe Tofacitinib off-label for AA, why hasn't there been a SINGLE person trying it out Androgenetic Alopecia with an off-label prescription for Androgenetic Alopecia? Makes no sense.

A member on another forum had this to say:

this is also been my point all along. they have tested it on people with AA, vitilgo, people that cannot grow eyebrows and I believe one other skin condition... All without an official clinical trial!

why can't they try it on people with Androgenetic Alopecia without a trial??

she even said in the interview, it either works or it won't and it won't take a long time to find out. so why not try it on a few people for a month or two, especially when the risk of side effects is solo topically.

screw this I'm making an appointment with my dermatologist next week to see what she thinks about this

And followed up with this:

just made my appointment for the 28th of December. I'll update you guys on what she says after the appointment
 

NewUser

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However, if physicians can prescribe Tofacitinib off-label for AA, why hasn't there been a SINGLE person trying it out Androgenetic Alopecia with an off-label prescription for Androgenetic Alopecia? Makes no sense.

Firstly, thank you for all your hard work on behalf of all of us, Hellouser. Much appreciated.

I think it would be difficult but not impossible to find a doctor willing to prescribe Tof pills to be taken orally for Androgenetic Alopecia. Their own lab test results reveal that the drug ingested orally for AA and psoriasis(the two auto-immune diseases may be linked) has grown human hair, but the drug is far more effective when applied topically on mice and, after gleaning this from NBC News article, I believe human AA patients? Insurance companies won't want to pay for 8 to 12 months of experimental use we can be sure. And so how many individual doctors without "skin in the game" other than their compassion for people will want to foot the bills themselves? Maybe a wealthy volunteer will find a doctor willing to prescribe it off label for a condition unrelated to an auto-immune disease, and then the same licensed doctor would have to verify the off label experimental results. I'm guessing they will choose to wait for IND approval before wading in, and they could have it sooner than later since it is already an FDA-approved drug with a safety record for systemic use. As Brett King said about it, it is a matter of short steps now.

Angela Christiano The surprise was when we started using the drugs on alopecia areata patients, when we used them topically the hair grew back much faster and more robustly than it did orally," Christiano told NBC News.

They already have a topical formulation that works albeit for AA. Guessing that Pfizer or whichever company has the patent on tof will want to include a pilot study for Androgenetic Alopecia and possibly enabling them to include pattern baldness on prescription labeling.

Brett King said, in June 2014, "I just can't advocate or promote that everybody go to their local doctor or their local dermatologist or rheumatologist and get hooked up with Xeljanz," he said, "but for the right person who can understand the potential risks , it might be the way to go."

I'd say it's probably on, and all that's needed are volunteers willing to try it at their own risk. $2000 a month for how many months, 8 to 12? Possible someone's trying it right now? By what I understand, Pfizer has deep pockets. Surely someone at Pfizer will want it tested for possible label approval as an Androgenetic Alopecia treatment. Big money possible for blue chip shareholders. Is it also possible that Christiano, Jahoda et al might want to develop their own topical cream for Androgenetic Alopecia and design or find their own JAK-inhibiting molecule(s) along the way? I think they have the talent to do just that. Or might they be having talks with Pfizer about cooperating on clinical tests for a topical formula. Time is money as they say, and I think Christiano and company will want to study Pfizer's patented drug some more, and them at Pfizer must be quite pleased about the possibilities. Deep pockets meet leading hair researchers.
 

F2005

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I believe so, there are patents on the jak inhibitors that mention topical formulations, but we dont know the vehicle or the concentration. But in the interview she mentions a high concentration, so perhaps we need a lot of it.... but the stuff is already WILDLY expensive.

However, if physicians can prescribe Tofacitinib off-label for AA, why hasn't there been a SINGLE person trying it out Androgenetic Alopecia with an off-label prescription for Androgenetic Alopecia? Makes no sense.

A member on another forum had this to say:



And followed up with this:

Amen to all of this, Hellouser. I wish they would at least TRY a topical version of this on some one with Androgenetic Alopecia. They certainly would not lack volunteers.

And once again, thanks so much Hellouser!!
 
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Swedishnyc

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Omg bla bla bla, everyone is going back and forth about pointless arguments. Why dont we try just get an interview with dr.christiano ? Anyone living in her area who could try schedual meet or phone interview on behalf of our memebers. Then we can get the awnsers. The simple solution is usualy the best
 

hellouser

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Omg bla bla bla, everyone is going back and forth about pointless arguments. Why dont we try just get an interview with dr.christiano ? Anyone living in her area who could try schedual meet or phone interview on behalf of our memebers. Then we can get the awnsers. The simple solution is usualy the best

I tried speaking with Dr. Christiano in person a couple of times at the Hair Congress...
 

distracted

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Omg bla bla bla, everyone is going back and forth about pointless arguments. Why dont we try just get an interview with dr.christiano ? Anyone living in her area who could try schedual meet or phone interview on behalf of our memebers. Then we can get the awnsers. The simple solution is usualy the best

You live in her area...She teaches at Columbia. Her contact information is available at this page http://vesta.cumc.columbia.edu/dermatology/index.php?id=amc65&type=research
 

Swedishnyc

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Thank you hellouser for trying to speak with her in miami , shame that you did not get an interview.

Hello "distracted", sadly im not in nyc anymore, im back in europe. But thank you for her contact email. I will certenly contact here about chances for an interview
 

distracted

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Thank you hellouser for trying to speak with her in miami , shame that you did not get an interview.

Hello "distracted", sadly im not in nyc anymore, im back in europe. But thank you for her contact email. I will certenly contact here about chances for an interview

I go to Colombia fairly often, but I am not knowledgable enough on the science behind hairloss to hold a conversation with her.
 

NewUser

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Originally Posted by Swedishnyc Thank you hellouser for all ur posts.
So This mean she allready has a topical cream tested and trialed??
Thank you


From what I can tell, yes to the first question. There were successful tests for growing hair using a topical solution for both lab test animals and people/patients with AA and some with AA and psoriasis.

And clinical trials for topical tofacitinib are currently underway.


allergicliving.com Currently in clinical trials, topical tofacitinib has not yet been approved by the FDA. Oral tofacitinib has only been tested in adults. “If a topical formulation of tofacitinib becomes available in the future,” Dr. King says, “then physicians will be able to evaluate more safely its use in children.”

 

F2005

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LOL, after hearing how long her and Spencer have been friends, it's no wonder she avoided interviews with someone from this site...

Haha, I thought of that too. And he hasn't interviewed her in years yet quite coincidentally right after Hellouser attends the Congress and attempts to interview her, Spencer finally conducts an interview. Hahaha. But anyway, apparently she said Tofa promotes robust hair growth in a topical form so this should REALLY be tried on people with Androgenetic Alopecia (topically). It makes no sense how it is only tried with conditions that only affect like 1% of the population (AA, vitiligo) but not with something like Androgenetic Alopecia which is soooooo much more common.
 

NewUser

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It makes no sense how it is only tried with conditions that only affect like 1% of the population (AA, vitiligo) but not with something like Androgenetic Alopecia which is soooooo much more common.

I think it's not so easy for people in medicine. Not all of them are strictly utilitarians. An example I googled: an elderly person is standing in the way between me and the last bag of apples on a shelf at the store. Should I shove them aside to make sure my family and I benefit from the apples and not the frail old person who lives alone? What if no one else was around to observe my utilitarian act? Would that make it any easier for me? Surely the greater good would be served? Is a more ideal outcome possible?
 

Swedishnyc

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I go to Colombia fairly often, but I am not knowledgable enough on the science behind hairloss to hold a conversation with her.


Oh thats awsome that you go to colombia. We should all try put simple questions together. But nothing too teqnical. We all just wants to know if it works for male pattern baldness or not. We Dont need to ask now how much the price would be or thecnical details or when it will be released, she wont be able to give that awnser anyway. We need to know if the mouse that she tested the topical cream on had been genetically enginered to have male pattern baldness, and then what the result was and what concentration % is needed. Thats it, nothing more.
 

F2005

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I think it's not so easy for people in medicine. Not all of them are strictly utilitarians. An example I googled: an elderly person is standing in the way between me and the last bag of apples on a shelf at the store. Should I shove them aside to make sure my family and I benefit from the apples and not the frail old person who lives alone? What if no one else was around to observe my utilitarian act? Would that make it any easier for me? Surely the greater good would be served? Is a more ideal outcome possible?

But there is no reason that tofacitinib cannot be tried on BOTH people with Androgenetic Alopecia and AA. Why does it have to be constantly tried on one while completely neglecting the other? Especially when one is so extremely more common than the other?
 

NewUser

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Topicals were rubbed on the backs for five days resulting in complete re-growth on the treated sides after 3 weeks. I don't believe mice would normally re-grow all of their hair in that short a time because as it is with human hair, not all mice hair will be in the same phase of hair cycle at the same time: i.e anagen, catagen or telogen. If left to grow back on its own, the mice hair would be patchy and sparse not thick and full after just 10 to 20 days. They believe JAK inhibitors are doing a lot more than just stopping the immune attack on hair follicles. Tof seems to be to hair what Miracle Gro is for plants, or at least with respect to Alopecia Areata, AU & AT - that's three hair loss conditions considered vexingly difficult for scientists to solve until recently, and they are still studying how JAK inhibitors work to re-grow hair for people with those conditions.

It's the fourth kind of hair loss, male & female pattern baldness, that no one knows if topical tofacitinib will work to re-grow hair. Apparently they are currently testing topical tofacitinib on patients with pattern baldness in clinical trials. With all the announcements about Christiano's work in hair loss having come out in recent years, I expect we will hear more about this sooner than later. I am hopeful for us all. Younger people here should be especially hopeful because they are seeing breakthroughs and announcements now unlike 10 or 15 years ago.
 

F2005

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Topicals were rubbed on the backs for five days resulting in complete re-growth on the treated sides after 3 weeks. I don't believe mice would normally re-grow all of their hair in that short a time because as it is with human hair, not all mice hair will be in the same phase of hair cycle at the same time: i.e anagen, catagen or telogen. If left to grow back on its own, the mice hair would be patchy and sparse not thick and full after just 10 to 20 days. They believe JAK inhibitors are doing a lot more than just stopping the immune attack on hair follicles. Tof seems to be to hair what Miracle Gro is for plants, or at least with respect to Alopecia Areata, AU & AT - that's three hair loss conditions considered vexingly difficult for scientists to solve until recently, and they are still studying how JAK inhibitors work to re-grow hair for people with those conditions.

It's the fourth kind of hair loss, male & female pattern baldness, that no one knows if topical tofacitinib will work to re-grow hair. Apparently they are currently testing topical tofacitinib on patients with pattern baldness in clinical trials. With all the announcements about Christiano's work in hair loss having come out in recent years, I expect we will hear more about this sooner than later. I am hopeful for us all. Younger people here should be especially hopeful because they are seeing breakthroughs and announcements now unlike 10 or 15 years ago.

Wow, awesome news!! I was not aware of this. Where did you read this?
 

NewUser

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Keep in mind that I am new to learning this stuff myself. And I pick up things from various web sites after reading quickly, but I am fairly certain that the word "trials" for topical tofacitinib to treat hair loss disorders in general are currently underway. As people have said here, there is a lot of money at stake with a cure for pattern baldness. They are surely testing for that right now as it takes time to observe results and produce data in order to warrant further studies and eventually a product and approval. Everyone is fully aware that money and profit are ultimately driving these studies. Everyone has bills to pay including researchers, themselves driven by commitments to medicine and compassion for people, and the people funding them.

"It's likely that the drugs that are so effective in enhancing hair growth in the mice could affect the same pathways in human follicles, suggesting they could induce new hair growth and extend the growth of existing hairs in humans." [...] "Experiments to address hair follicles affected by hair loss disorders are under way."

Currently in clinical trials, topical tofacitinib has not yet been approved by the FDA.

So they are taking the scientific approach. This really is the best way because if it turns out that JAK inhibitors do not solve pattern baldness, they will at least have more understanding of the pathways that actually affect hair growth and possibly leading them to an effective treatment.

There are all kinds of unknowns that will be answered with experiments currently underway. Of course the most direct answer to our questions will surely be known after pilot studies of topical tof applied directly to a small area of scalp affected by Androgenetic Alopecia. Every engineering professional knows that if you find one leak in a water hose or electrical path, you plug that leak or splice that wire and test it right away for a working path not continue on down the line looking for more leaks or breaks in the line which may or may not exist. A lot can be learnt from testing and trial and error which are valid methods of inquiry.

And now I think that it is not just normal mice with normal hair used in all experiments. Apparently Christiano's colleagues have done experiments on mice with alopecia areata-affected skin tissue grafted on the backs. They want to know more about an into an auto-immune disease affecting the skin and scalp referred to as CANDLE which results in hair loss and skin lesions.

Topical Tofacitinib (for atopic dermatitis) success at Phase II Clinical July 2015

Ruxolitinib Cream Restores Hair Growth in Yale Study
So in these instances, when hair follicles enter resting state due to auto-immune attack, topical Ruxolitinib and Toficitinib are shown to be effective in re-growing hair. And that is a fairly extreme situation when the body's immune cells turn against hair follicles stopping growth. Could it be that the drug works regardless of what causes follicles to enter resting state? Similarly, people and animals can be tired and fall asleep by a number of causes such as a normal sleep-wake cycle, sleep deprivation, drug-induced sleep, anesthesia etc or an extreme situation like carbon monoxide poisoning. And the "cure" is generally the same for all of those conditions: oxygen and rest.

- - - Updated - - -

However, if physicians can prescribe Tofacitinib off-label for AA, why hasn't there been a SINGLE person trying it out Androgenetic Alopecia with an off-label prescription for Androgenetic Alopecia? Makes no sense.

By what I've read, physicians certainly can prescribe it off-label. The problem is the cost of the drug - it's expensive. The good news, according to Christiano, is that there are 2 oral JAK inhibitors with established safety records already approved, and that there are several more in the pipeline. I believe she means that if more JAK inhibitors come to market, prices will eventually drop. And, she says, there are all kinds of incentives for drug companies to pursue JAK-inhibitors/drugs because there will be several indications for the drug, like plaque psoriasis, rheumatoid arthritis and, in all likelihood, alopecia areata, A, AU and AT and possibly Androgenetic Alopecia.

Christiano also mentioned that buried deep within the paper she and Jahoda published is a method for delivering JAK inhibitors deep enough into the dermis for optimal effect by applying JAK-I to DP cells which are cultured in 3D spheres. When they did this, it increased induction and DP signaling by anywhere from 25% to 50% resulting in much more hair growth in, I believe, mice. So if any physician-prescribed versions of the compound do not work for Androgenetic Alopecia the same as it has for the other three hair loss disorders, I think there might still be success with Christiano's and Jahoda's invention which will have to be tested in registered clinical trials for several reasons and a patent being one of them.

I also gather that Christiano is hopeful for other drugs in the pipeline namely setipiprant.
 

F2005

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Keep in mind that I am new to learning this stuff myself. And I pick up things from various web sites after reading quickly, but I am fairly certain that the word "trials" for topical tofacitinib to treat hair loss disorders in general are currently underway. As people have said here, there is a lot of money at stake with a cure for pattern baldness. They are surely testing for that right now as it takes time to observe results and produce data in order to warrant further studies and eventually a product and approval. Everyone is fully aware that money and profit are ultimately driving these studies. Everyone has bills to pay including researchers, themselves driven by commitments to medicine and compassion for people, and the people funding them.





So they are taking the scientific approach. This really is the best way because if it turns out that JAK inhibitors do not solve pattern baldness, they will at least have more understanding of the pathways that actually affect hair growth and possibly leading them to an effective treatment.

There are all kinds of unknowns that will be answered with experiments currently underway. Of course the most direct answer to our questions will surely be known after pilot studies of topical tof applied directly to a small area of scalp affected by Androgenetic Alopecia. Every engineering professional knows that if you find one leak in a water hose or electrical path, you plug that leak or splice that wire and test it right away for a working path not continue on down the line looking for more leaks or breaks in the line which may or may not exist. A lot can be learnt from testing and trial and error which are valid methods of inquiry.

And now I think that it is not just normal mice with normal hair used in all experiments. Apparently Christiano's colleagues have done experiments on mice with alopecia areata-affected skin tissue grafted on the backs. They want to know more about an into an auto-immune disease affecting the skin and scalp referred to as CANDLE which results in hair loss and skin lesions.

Topical Tofacitinib (for atopic dermatitis) success at Phase II Clinical July 2015

Ruxolitinib Cream Restores Hair Growth in Yale Study
So in these instances, when hair follicles enter resting state due to auto-immune attack, topical Ruxolitinib and Toficitinib are shown to be effective in re-growing hair. And that is a fairly extreme situation when the body's immune cells turn against hair follicles stopping growth. Could it be that the drug works regardless of what causes follicles to enter resting state? Similarly, people and animals can be tired and fall asleep by a number of causes such as a normal sleep-wake cycle, sleep deprivation, drug-induced sleep, anesthesia etc or an extreme situation like carbon monoxide poisoning. And the "cure" is generally the same for all of those conditions: oxygen and rest.

- - - Updated - - -



By what I've read, physicians certainly can prescribe it off-label. The problem is the cost of the drug - it's expensive. The good news, according to Christiano, is that there are 2 oral JAK inhibitors with established safety records already approved, and that there are several more in the pipeline. I believe she means that if more JAK inhibitors come to market, prices will eventually drop. And, she says, there are all kinds of incentives for drug companies to pursue JAK-inhibitors/drugs because there will be several indications for the drug, like plaque psoriasis, rheumatoid arthritis and, in all likelihood, alopecia areata, A, AU and AT and possibly Androgenetic Alopecia.

Christiano also mentioned that buried deep within the paper she and Jahoda published is a method for delivering JAK inhibitors deep enough into the dermis for optimal effect by applying JAK-I to DP cells which are cultured in 3D spheres. When they did this, it increased induction and DP signaling by anywhere from 25% to 50% resulting in much more hair growth in, I believe, mice. So if any physician-prescribed versions of the compound do not work for Androgenetic Alopecia the same as it has for the other three hair loss disorders, I think there might still be success with Christiano's and Jahoda's invention which will have to be tested in registered clinical trials for several reasons and a patent being one of them.

I also gather that Christiano is hopeful for other drugs in the pipeline namely setipiprant.

The thing is though, you didn't link an article that mentioned any definitive proof that they are testing Tofa in people with Androgenetic Alopecia. Just that it is being tested in people with hair disorders, which we all know they've been doing with AA. Throughout the years, we've all know how much supposed money there would be in a cure for Androgenetic Alopecia, yet there are so very few attempts to do anything to cure it.
 

NewUser

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I'm satisfied knowing that topical Tof has been shown to work very well on alopecia areata test patients. People who were totally bald for years now have full heads of hair? That is miraculous. They've tested it on shaved lab mice, lab mice with human tissue and hair grafts, and they've tested it on human scalps affected by three of the four major hair loss disorders.

October 23, 2015 "What we've found is promising, though we haven't yet shown it is effective for male pattern baldness," said Dr. Christiano. "More work needs to be done to test formulations of JAK inhibitors specially made for the scalp to determine whether they can induce hair growth in humans."

The Christiano-Jahoda paper was published just weeks ago. They can't just whip up a batch of topical Tof and begin testing on 30 ppl with Androgenetic Alopecia. A physician can do it off-label for patients with money to burn, but Christiano and Jahoda? They are cash-starved researchers and would need to apply for regulatory approval. Who pays for that? Researchers like Christiano have full-time jobs, and their research is tied to funding for specific purposes. They are accountable to someone. Christiano did say that they have taken this as far as they can without a partner with deep pockets, like big pharma.

Like she says, their paper only came out a few weeks ago, so let's not give up yet. The good news, she says, is that there are already two JAK-inhibitors on the market and more in the pipeline. This means the price will come down eventually. The other good news is that JAK inhibitors, a relatively new discovery, have a growing list of indications for use, which is more incentive for pharmaceutical companies to invest in and develop them. Christiano says the time-to-fail for knowing if JAK-I is a cure for Androgenetic Alopecia is a short one. "It's an active field", and "there is momentum" to discover if JAK-I is a cure for Androgenetic Alopecia and for someone taking the lead.

It's a couple of phase 1 trials with low risk. People know how to do topical delivery, and people know how to do imaging for a really good hair loss trial. The mechanics are there for a solid trial.
 
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