Aclaris Call Tomorrow - Ask Your Questions

[Pavi]

LOL at asking if forum members have had success using a topical JAK. Just do the research if you think it works. What a joke.

LOL at asking if forum members have had success using a topical JAK. Just do the research if you think it works. What a joke.

That seemed so weird to me too lol seemed like it was amateur hour over at Aclaris

 

[hellouser]

LOL at asking if forum members have had success using a topical JAK. Just do the research if you think it works. What a joke.

I still can't figure out why some doctors handed out Tofacitinib for case studies for people with AA but ignored Androgenetic Alopecia.

THAT is a joke!

 

[Grasshüpfer]

LOL at asking if forum members have had success using a topical JAK. Just do the research if you think it works. What a joke.

I get the feeling they called mainly to ask this question.
@Admin Do you think there's a hidden hint to try it?

 

[NewUser]

Thank you Admin for getting us this interview. I think a number of things can be assumed from their lack of communication.

I am not good with legal stuff so I want to ask what's up with these legal stuff that making Aclaris not talk ?

Tighter SEC rules since 2008 for sure. They don't want stocks pumping up by "insider" information or by false information, like happened leading up to 2008. It would be nice for Aclaris' shareholders if CEOs and bankers could act as stock promoters and vice versa. That's not supposed to happen now. It would be nice if they could pump-up their own stocks and sell high whether they have an AA (and possibly an Androgenetic Alopecia) treatment or not. I think they will at least have a legit treatment for AA, AU and AT. They surely have something in the works.

 

[Swoop]

That seemed so weird to me too lol seemed like it was amateur hour over at Aclaris

Beyond amateurs lol.

They have nothing only some results on a useless mice model (speaking about Androgenetic Alopecia only here offc.)

Whatever though.

 

[Stupidon]

I still can't figure out why some doctors handed out Tofacitinib for case studies for people with AA but ignored Androgenetic Alopecia.

THAT is a joke!

Actually it's not, given the price and that there is no solid background on it.

 

[hellouser]

Actually it's not, given the price and that there is no solid background on it.

The same excuses could have been used before trying it on AA.. then it worked.

 

[InBeforeTheCure]

The same excuses could have been used before trying it on AA.. then it worked.

Christiano and her colleagues pursued JAK inhibitors for AA based on GWAS results, or by "reading the genetic tea leaves" as she calls it.

Little was known about the genetics of the disease at that time other than a slight increased risk with a family history of autoimmune disorders. For Christiano, whose hair has since regrown, the way forward was clear — a genome-wide association study (GWAS) to let the genetics of the disease highlight potential mechanisms to target with treatment. “We had to read the genetic tea leaves and let them direct the research,” she says.

By 1999, Christiano and colleagues, with help from the US National Alopecia Areata Foundation (NAAF), had banded together five major clinical research centres and began to interview and phenotype several thousand patients. Their findings, published in 2010, identified eight regions with significant and specific associations with alopecia areata[2].

“It opened up an important collaboration for us,” says Christiano, who took the results to an immunologist colleague at Columbia, Raphael Clynes. “We’re just simple geneticists but he looked at the pathways indicated by the GWAS — IL [interleukin]-2, IL-15, IFN [interferon]-y — and said ‘this is just diabetes of the hair follicle’.”

It was an important shift in Christiano’s understanding of what alopecia areata is. “For years, people assumed alopecia was a relative of psoriasis. Most trials just tested existing psoriasis drugs and we wondered why they didn’t work. We never thought about diabetes or coeliac or rheumatoid arthritis but that’s the group of autoimmune diseases we clearly align with.”

In all of these autoimmune diseases a specific autoantigen, or danger signal, is expressed to call in the damaging immune response. “HLA [the human leukocyte antigen system gene complex] was our top hit,” says Christiano of her GWAS findings, “but these are the nuts and bolts of the immune response so we expect them to be upregulated in all autoimmune disorders. What gets geneticists excited are the ones that are unique to a disorder.”

The second biggest hit was for ULBP, a gene unique to alopecia and one, it turned out, that codes for a danger signal expressed by hair follicles in alopecia.

Targeted treatment
When the ULBP-encoded surface protein binds to a killer receptor on the T cell it engages an intracellular cascade that destroys the hair follicle dermal sheath cells and forces hair growth out of its cycle. Several of these intracellular pathways go through tyrosine kinases called janus kinases (JAKs), particularly JAKs 1–3. By inhibiting JAKs 1 and 2, as Christiano and colleagues did with the myelofibrosis drug ruxolitinib, you negate the effect of the danger signal and stop the disease in its tracks.

They’ve tested another JAK inhibitor called tofacitinib, too, which is FDA-approved in the United States for the treatment of rheumatoid arthritis. But as with ruxolitinib, the at-first promising results taper off once the drug is stopped.

Link: http://www.pharmaceutical-journal.c...for-alopecia-areata-patients/20201092.article

GWAS done on Androgenetic Alopecia look nothing like the ones done on AA. AR is the most significant association with Androgenetic Alopecia, and there are also a ton of associations with genes related to hair follicle development and cycling as well. There isn't the same kind of theoretical indication that JAK inhibitors could work on Androgenetic Alopecia, but nonetheless they're going to trial it on Androgenetic Alopecia and we'll see how it goes.

 

[NewUser]

Concretely, Have they seen regrowth on someone?

Yes they have, for a small number of people with a vexingly difficult-to-solve hairloss disorder. These are hairloss disorders for which neither an ocean of min nor a ton of white powder finasteride would grow a single hair for.
Before Christiano's serendipitous discovery, people with alopecia areata, AU and AT had less hope for an effective treatment than those of us with Androgenetic Alopecia. Imagine having no hair anywhere on your body. No eyebrows nor beard let alone a horseshoe of hair.

One thing I've noticed is that the NAAF is a cohesive foundation that helped fund 12 of geneticist Angela Christiano's earliest research studies on AA. Christiano, Jahoda, Higgins etc are not wealthy researchers but starving researchers. It takes money to run clinical trials, and as a researchers and not a medical doctor, she can't just whip up a batch of topical or oral tofacitinib and run a secret trial for Androgenetic Alopecia. Tof and Rux already had label indications for conditions related to immune disorders, therefore it was reasonable to believe they might do something for AA sufferers but not Androgenetic Alopecia in the same way no one is interested in trialing the drugs finasteride or minoxidil for AA patients. It simply would not follow unless at least one AA patient stepped forward to reveal those old drug discoveries might do a single bit of good for any of the immune-related alopecias. Rux and Tof are different in that they act on several important hair growth signaling pathways according to Christiano's research.

So that's three out of four major hairloss disorders down, or not nearly as hopeless to solve as before, and one to go.

 

[NewUser]

I know a lot of people have high hopes for JAK inhibitors because of Dr Christiano's work, but i can tell you Dr Christiano is not all the media cracks her up to be. I'm pretty sure she just she got lucky with seeing results of JAK inhibitors acting on AA and all of a sudden she got a spotlight on her like she knows what she's doing.

She did get lucky and admitted it was a serendipitous discovery. It's how progress in science is made, by doing things differently in unpredictable ways. And with science you tend to have to be good in order to get lucky.

And so *now* everyone wants to know if JAKinibs will work for Androgenetic Alopecia. Aclaris, and using Christiano's research as a basis, will answer that question for us. Now it is a reasonable question to merit doing clinical trials.

 

[NewUser]

I can't actually see how JAK inhibitors could have any impact on Androgenetic Alopecia. If Androgenetic Alopecia is caused by hair follicles' high sensitivity to DHT hormones, how would a drug that targets immune system T-cells contribute to fighting that at all?

According to Cotsarelis and other renowned hair biologists within the last 5 years, AA is considered a nonscarring alopecia and reversible. Androgenetic Alopecia is also considered a nonscarring alopecia, and now they think Androgenetic Alopecia might also be reversible.

And Christiano's paper published October of last year reveals that jakinibs do more to affect hair growth than suppressing janus kinase.

 

[FootyStar]

According to Cotsarelis and other renowned hair biologists within the last 5 years, AA is considered a nonscarring alopecia and reversible. Androgenetic Alopecia is also considered a nonscarring alopecia, and now they think Androgenetic Alopecia might also be reversible.

And Christiano's paper published October of last year reveals that jakinibs do more to affect hair growth than suppressing janus kinase.

I see now, thanks for clarifying.

It would be awesome if JAK inhibitors worked for multiple forms of alopecia so it could kind of be a one-stop treatment for hair loss.

 

[hidden]

what an irresponsible statement from dr christiano when she asked if forum users tried the topical jak and asked for photos, now many will rush to try this dangerous drug which will f*** up the immunity...., total disappointment for this necessary call, i hope Aclaris guys are reading this thread to see that they screwed up big time...

 

[Blackber]

what an irresponsible statement from dr christiano when she asked if forum users tried the topical jak and asked for photos, now many will rush to try this dangerous drug which will f*** up the immunity...., total disappointment for this necessary call, i hope Aclaris guys are reading this thread to see that they screwed up big time...

The drug does hamper the immune system it's already FDA approved and people on other hair loss forums have already tried it, so not sure why you're trying to rile people up.

I think it's ridiculous they agreed to do an interview then stopped it from being posted. You say they "messed up big time" but if the drug does work you'll still use it....

 

[hidden]

The drug does hamper the immune system it's already FDA approved and people on other hair loss forums have already tried it, so not sure why you're trying to rile people up.

I think it's ridiculous they agreed to do an interview then stopped it from being posted. You say they "messed up big time" but if the drug does work you'll still use it....

U should read more on the jaks approved by fda and their uses and concentration...

See the alopeciaexperiment insta account for the AA girl how she never used under constant dr supervision with checking blood levels each month... theses are potent drugs

 

[NewUser]

I can't actually see how JAK inhibitors could have any impact on Androgenetic Alopecia. If Androgenetic Alopecia is caused by hair follicles' high sensitivity to DHT hormones, how would a drug that targets immune system T-cells contribute to fighting that at all?

I think they'd been down the same road with AA before with cortisone. If stopping inflammation alone would grow hair for AA sufferers, then cortisone should work. Cortisone doesn't cure AA, tho. Jakinibs doing something more to affect hair growth than curbing an autoimmune attack on hair follicles.

 

[Swoop]

I think they'd been down the same road with AA before with cortisone. If stopping inflammation alone would grow hair for AA sufferers, then cortisone should work. Cortisone doesn't cure AA, tho. Jakinibs doing something more to affect hair growth than curbing an autoimmune attack on hair follicles.

https://www.researchgate.net/public..._treatment_of_alopecia_totalis_or_universalis

No cortisone, however no JAK either, prednisone and methotrexate;

Treatment of severe alopecia areata (AA) remains difficult. To assess the tolerance and efficacy of methotrexate (MTX) in the treatment of severe long-term AA, we retrospectively evaluated 22 patients with AA totalis or universalis with a mean duration of 11.0 +/- 8.8 years who were treated with MTX either alone (n = 6) or associated with low doses of oral prednisone (n = 16). MTX was given at an initial weekly dosage of 15 mg (n = 3), 20 mg (n = 9), or 25 mg (n = 10). Oral prednisone was given at an initial dosage of 10 mg/d in one patient and 20 mg/d in 15 patients. In all, 14 patients (64%) achieved a total recovery including 3 of 6 patients treated by MTX alone and 11 of 16 who had received the combined treatment.

 

[NewUser]

https://www.researchgate.net/publication/6783624_The_use_of_methotrexate_alone_or_in_combination_with_low_doses_of_oral_corticosteroids_in_the_treatment_of_alopecia_totalis_or_universalis

No cortisone, however no JAK either, prednisone and methotrexate;

Treatment of severe alopecia areata (AA) remains difficult.

Hmm, sounds promising. And In this study of 31 patients with AA treated with methotrexate, about the same significantly large percentage achieved regrowth.

Regrowth was more likely to have occurred in those with disease duration of less than 5 years, those treated concomitantly with systemic corticosteroids, and those with multifocal disease. Relapse occurred in a third of patients who had <50% regrowth.​

On the other hand, Brett King's 25 year-old patient was diagnosed with alopecia areata when he was 2.
With respect to AA they are quoting a success rate of 75% with jakinibs and want to find out why the other 25% are non-responders.

Xing et al said, in 2014, "Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition." 3 out of 3 patients, 100%, achieved nearly complete regrowth after just 5 months.

Tofacitinib treatment promotes growth of human HFs

We further analyzed the effects of JAK inhibition on hair shaft elongation using the human HF organ culture model. Individual HFs were microdissected from human adult scalp tissue and cultured with vehicle control, ruxolitinib, and tofacitinib (Fig. 3B). We found that treatment with JAK inhibitors significantly increased the length of hair shafts when treated with ruxolitinib and tofacitinib, indicating a positive effect on the rate of hair elongation (P = 0.023 and P = 0.025 for tofacitinib and ruxolitinib, respectively).

Christiano and Cotsarelis say both AA and Androgenetic Alopecia are categorized as nonscarring alopecias, and that AA is now considered reversible. They think Androgenetic Alopecia may also be reversible. Both hairloss disorders have one thing in common, and that is hair follicles are stuck in telogen. Christiano believes that whatever the disorder, AA or Androgenetic Alopecia, both should benefit by the effect of pushing HF from telogen to anagen growth.

 

[Swoop]

Christiano and Cotsarelis say both AA and Androgenetic Alopecia are categorized as nonscarring alopecias, and that AA is now considered reversible. They think Androgenetic Alopecia may also be reversible. Both hairloss disorders have one thing in common, and that is hair follicles are stuck in telogen. Christiano believes that whatever the disorder, AA or Androgenetic Alopecia, both should benefit by the effect of pushing HF from telogen to anagen growth.

Cotsarelis doesn't believe that that male pattern baldness can be completely reversed;

“Cotsarelis says that in gauging future prospects for alopecia treatment, it’s important to have realistic expectations. “I’d hate to use the word cure, because I don’t think male-pattern baldness can be completely reversed,” he says. “Instead, we’ll develop different treatments, and as with other personalized therapies in medicine, some will work better in various subgroups than others.”

Also, Androgenetic Alopecia might not be categorized as a nonscarring alopecia but that is a fallacious statement because scarring does happen sometimes in Androgenetic Alopecia patients due to fibrosis deposits that can damage and even destroy the whole hair follicle structure. Per definition this already makes Androgenetic Alopecia irreversible in some people. Refer to the study of Domyati et al (1).

Also AA and Androgenetic Alopecia are completely different. AA is auto-immune driven primarily ,while Androgenetic Alopecia is not, Androgenetic Alopecia is a beast compared to AA. That's also why observations have shown already for many years that AA is reversible especially when patients take immunomodulatory compounds like cyclosporine, heavy glucocorticoids, methotrexate etc. You have just linked a study yourself that shows this and I just showed you one. There are many other case reports and studies of reversal with AA. They now have JAKS, they probably do a (way) better job at it, well nice for the patients with AA. They can broaden their options, absolutely great.

But yeah time will tell you anyway. I would love to slap some drug on my scalp and that regrowth would follow, it's just highly unrealistic.

 

[Ikkaku]

Also, Androgenetic Alopecia might not be categorized as a nonscarring alopecia but that is a fallacious statement because scarring does happen sometimes in Androgenetic Alopecia patients due to fibrosis deposits that can damage and even destroy the whole hair follicle structure. Per definition this already makes Androgenetic Alopecia irreversible in some people. Refer to the study of Domyati et al (1).

Someone said me that we can destroy fibrosis.
You have to use castor oil + DMSO.