Follica - Good News!

[Moomin]

Well well well Lidocaine an EGFR inhibitor has an affect on Tyrisone Kinase which in turn has a strong affect on epithelial cell formation, who'd a thunk it. I wonder if there are any more EGFR inhibitors that have the same affect?

 

[first]

Getfitinib, erlonitib, and lefloumonide are all associated with a lung disease in a relatively rare side effect. .

I thought that was a side effect only if you already had lung cancer. Are you sure about it being a side effect otherwise?

 

[LinuxCavalier]

Getfitinib, erlonitib, and lefloumonide are all associated with a lung disease in a relatively rare side effect. .

I thought that was a side effect only if you already had lung cancer. Are you sure about it being a side effect otherwise?

i think it is probably much more common for people with pre-existing lung problems. From astrazeneca's press release on drug announcement:

"Interstitial Lung Disease (ILD) is a known complication of lung cancer and has been observed in about 1 per cent of patients taking IRESSA."


Also found this:

Cases of interstitial lung disease (ILD) have been observed in patients receiving IRESSA at an overall incidence of about 1%. Approximately 1/3 of the cases have been fatal. The reported incidence of ILD was about 2% in the Japanese post-marketing experience, about 0.3% in approximately 23,000 patients treated with IRESSA in a US expanded access program and about 1% in the studies of first-line use in NSCLC (but with similar rates in both treatment and placebo groups). Reports have described the adverse event as interstitial pneumonia, pneumonitis and alveolitis. Patients often present with the acute onset of dyspnea, sometimes associated with cough or low-grade fever, often becoming severe within a short time and requiring hospitalization. ILD has occurred in patients who have received prior radiation therapy (31% of reported cases), prior chemotherapy (57% of reported patients), and no previous therapy (12% of reported cases). Patients with concurrent idiopathic pulmonary fibrosis whose condition worsens while receiving IRESSA have been observed to have an increased mortality compared to those without concurrent idiopathic pulmonary fibrosis

i still wouldn't touch it until we know more about it

 

[michael barry]

Linux,

You make very valid points believe me. Ive considered it and would be lying if I told you I was unconcerned.


However, Im relatively young, in good shape, have never smoked, have never had chemo or anything like that, and Im only probably going to be taking this stuff for 7 or 8 days.....10 tops. Thats if it actually comes in the damned mail (Ive ordered Arava twice and it never got here). There are two other guys I know who are going to take the egf antagonists internally. So we will be the "gunieau pigs" for everyone (LOL). I'll probably be trying it within the next couple of weeks.

 

[chancer]

Michael,

We All know your name so well by now and your intelegent and calculated posts...

but we dont know your scalp!! please make sure you take some good before and after pics, if need be have that days national newspaper in the background to back you up...

Good luck Mate.... we are all right behind you!!

 

[harold]

Well well well Lidocaine an EGFR inhibitor has an affect on Tyrisone Kinase which in turn has a strong affect on epithelial cell formation, who'd a thunk it. I wonder if there are any more EGFR inhibitors that have the same affect?

...OK I dont want to start everything up but my curiosity has the better of me - what did you mean by the above comments?
hh

 

[michael barry]

Harold,

Had you seen this:

Lidocaine is an egf inhibitor



Anesthesiology. 2004 May;100(5):1206-10.

Lidocaine inhibits tyrosine kinase activity of the epidermal growth factor receptor and suppresses proliferation of corneal epithelial cells.
BACKGROUND: Although lidocaine is recognized as an excellent topical corneal analgesic, its toxic effect on corneal epithelial cells limits its use during corneal epithelial wound healing. Mechanism of the impairment of corneal reepithelialization with lidocaine, however, has not been evaluated. The authors' previous study revealed that lidocaine inhibits the activity of tyrosine kinase receptors through the interaction with specific amino acid sequences around autophosphorylation sites, including acidic, basic, and aromatic amino acids. Epidermal growth factor receptor (EGFR), a tyrosine kinase receptor with an important role in epithelial cell proliferation after corneal wounding, also possesses these amino acids sequences around autophosphorylation sites. The authors hypothesized that lidocaine would suppress tyrosine kinase activity of EGFR and would impair corneal epithelial cell proliferation. METHODS: To investigate the effect of lidocaine (4 microM-40 mM) on epidermal growth factor (EGF)-stimulated autophosphorylation of EGFR, the authors studied purified EGFR in microtubes. They cultured human corneal epithelial cells (HCECs) with EGF and lidocaine to investigate the effect of lidocaine on cell proliferation and on autophosphorylation of EGFR in HCECs. RESULTS: Lidocaine (> or =400 microM) significantly suppressed EGF-stimulated autophosphorylation of the purified EGFR. In the HCEC study, EGF alone stimulated cell proliferation and increased autophosphorylation of EGFR in HCECs. Lidocaine (> or = 400 microM) significantly suppressed both the proliferation of HCECs promoted by EGF and EGF-stimulated autophosphorylation of EGFR. CONCLUSION: Lidocaine directly inhibits tyrosine kinase activity of EGFR and suppresses the corneal epithelial cell proliferation.

PMID: 15114219 [PubMed - indexed for MEDLINE]



I highlighted the one part of that info that might be of some concern. Whether the effect on epilithial cells would impair the whole proess in some unforseen way..... You can buy lidocaine gels though. I have a tube.

 

[harold]

Harold,

Had you seen this:

Lidocaine is an egf inhibitor



Anesthesiology. 2004 May;100(5):1206-10.

Lidocaine inhibits tyrosine kinase activity of the epidermal growth factor receptor and suppresses proliferation of corneal epithelial cells.
BACKGROUND: Although lidocaine is recognized as an excellent topical corneal analgesic, its toxic effect on corneal epithelial cells limits its use during corneal epithelial wound healing.



I highlighted the one part of that info that might be of some concern. Whether the effect on epilithial cells would impair the whole proess in some unforseen way..... You can buy lidocaine gels though. I have a tube.

Yeah I saw that. I am pretty certain the toxic effect they refer to is due to the inhibition of EGF and not due to some inherently cytotoxic effect or whatever. In other words I think that term was badly chosen. I will try to catch the whole study though and see exactly what it says. But thats very much what it suggests to me.
hh

 

[Orin]

So would lidocaine be considered a synthetic EGFR-inhibitor?

Great it if is, but I doubt it's very effective. People are bound to have been smearing that stuff on scrubs and open wounds before (it being used for pain-management). Seems like we should have heard about it growing hair by now, unless it's a new drug (I'm not american, never heard of it before).

Thought that should not stop anyone from making a test-patch with it, just so we know.

 

[michael barry]

Here are all of the EGF-antagonists mentioned in the second patent: (we think getfitinib is what they intend to use due to a couple of very strange hairgrowth photos associated with it----one with thick hair growing on someones nose and one with a guy growing alot of hair right in the middle of LONG bald scalp----dark hair in both cases, even though the guy had greyish hair on his fringe).



In another embodiment, the inhibitor of an EGF or an EGF receptor is panirumumab. In another embodiment, the inhibitor is AG1478. In another embodiment, the inhibitor is nimotuzumab. In another embodiment, the inhibitor is an antibody that binds EGF or EGFR. In another embodiment, the inhibitor is HuMax-EGFR® (Genmab, Copenhagen, Denmark). In another embodiment, the inhibitor is cetuximab. In another embodiment, the inhibitor is IMC 11F8. In another embodiment, the inhibitor is matuzumab. In another embodiment, the inhibitor is SC 100. In another embodiment, the inhibitor is ALT 110. In another embodiment, the inhibitor is PX 1032. In another embodiment, the inhibitor is BMS 599626. In another embodiment, the inhibitor is MDX 214. In another embodiment, the inhibitor is PX 1041. In another embodiment, the inhibitor is any other inhibitor of an EGF or an EGF receptor known in the art. Each possibility represents a separate embodiment of the present invention.

[00064] In another embodiment, the compound or factor that promotes a differentiation of an uncommitted epidermal cell into a HF cell is an inhibitor of a tyrosine kinase activity of an EGF receptor. In another embodiment, the inhibitor is gefitinib. In another embodiment, the inhibitor is

P-7628-PC erlotinib. In another embodiment, the inhibitor is canertinib. In another embodiment, the inhibitor is leflunomide. In another embodiment, the inhibitor is A77 1726. In another embodiment, the inhibitor is pelitinib. In another embodiment, the inhibitor is ZD 1839. In another embodiment, the inhibitor is CL 3877S5. In another embodiment, the inhibitor is EKI 785. In another embodiment, the inhibitor is vandetanib. In another embodiment., the inhibitor is any other inhibitor of a tyrosine kinase activity of an EGF receptor known in the art. Each possibility represents a separate embodiment of the present invention.

[00065] In another embodiment, the EGF or EGFR antagonist is a carboxypeptidase inhibitor from potato (PCI) protein or a homologue,, fragment or mimetic thereof. In another embodiment, the EGF or EGFR antagonist is a sprouty protein or a homologue, fragment or mimetic thereof. In another embodiment, the EGF or EGFR antagonist is an Argos protein or a homologue, fragment or mimetic thereof. In another embodiment, the EGF or EGFR antagonist is a lefty protein or a homologue, fragment or mimetic thereof. In another embodiment, the EGF or EGFR antagonist is an antibody that recognizes EGF or EGFR, or a fragment or mimetic thereof. Bi another embodiment, the EGF or EGFR antagonist is small molecule inhibitor that binds and reduces the activity of EGF or EGFR. In another embodiment^ the EGF or EGFR antagonist is CRMl 97. In another embodiment, the EGF or EGFR antagonist is IMC-C225 (ImClone Systems, New York. NY). In another embodiment, the EGF or EGFR antagonist is any other antagonist of EGF or EGFR known in the art. Each possibility represents a separate embodiment of the present invention.

 

[Moomin]

Alright I have a practical question.

What are we using to get Lithium (in whatever form) into the skin. It seems so far that we are using ethanol to carry Lithium through to the skin.

Is there anything better than ethanol for this activity, I've heard DMSO is excellent at this but there may also be some safety issues surrounding it. Also, I understand that Lithium Chloride is very easily absorbed making it, potentially, a better candidate than the orotate (incindentally lithium chloride in powder form is relatively easy to purchase it would seem).

Also does anyone have any theories as to what concentrations / amounts of lithium might be applied.

 

[Matt27]

Someone posted over on HLH that Follica is looking for volunteers to test and monitor dermabrasian on bald scalp in humans. Here's the link:

http://www.hairlosshelp.com/forums/mess ... adid=80161

 

[first]

Alright I have a practical question.

What are we using to get Lithium (in whatever form) into the skin. It seems so far that we are using ethanol to carry Lithium through to the skin.

Is there anything better than ethanol for this activity, I've heard DMSO is excellent at this but there may also be some safety issues surrounding it. Also, I understand that Lithium Chloride is very easily absorbed making it, potentially, a better candidate than the orotate (incindentally lithium chloride in powder form is relatively easy to purchase it would seem).

Also does anyone have any theories as to what concentrations / amounts of lithium might be applied.

I have Lithium Chloride and DMSO at home but I have not used it yet, still looking for the right EGF inhibitor for the second part of my tests. However, an approximate lithium concentration would be around 3-10%. With DMSO you will most definitely get some of that into your blood stream, however, it shouldn't have any major effect with such a low dosage for a short period of time.

 

[chancer]

Someone posted over on HLH that Follica is looking for volunteers to test and monitor dermabrasian on bald scalp in humans. Here's the link:

http://www.hairlosshelp.com/forums/mess ... adid=80161

Hmm... Thats interesting, though i don’t know if its good news and bad news....

In no way is any of that advertising for volunteers related to Follica from the links...

But the guy on the other hair forum does state that it was follica who sent him the info in the email. So they are using a 3rd party - in this case a medical school called Hardvard to promote it for them and take the heat off the situation. Though it must be said, if its just mastering the dermabrasion then our realistic hopes have taken a backward step. surely they have input from the worlds most advance dermatologists on this, i would of thought this part of the process is relatively simple. I though follica would be more worried about finding the best and most optimum formula to conjure up out of all the medical ingredient drugs that is on their lab table.

i mean, why dont they pay us a visit, theres a few of us already learning to dermabrade ourselves in areas around 1 inch diameter.

Back to the drawing board... Michael Barry illustrated all the EGF inhibitors we know of... guys any of you, doesnt matter if your new to all this, or if you have been studying hair loss for decades; if you have a some spare time, start googling all those EGF inhibitors highlighted and lets see what we can find out !! Doesn’t matter if you don’t understand it because some of the experienced guys on here can digest it and put it into lemans terms... Copy and paste is a wonderful tool.... united and together we can do so much....

Heres our research list...
Panirumumab
AG1478
HuMax-EGFR® (Genmab, Copenhagen, Denmark)
cetuximab
IMC 11F8
ALT 110
PX 1032
BMS 599626
MDX 214
P-7628-PC
erlotinib
canertinib
leflunomide
A77 1726
pelitinib
ZD 1839
EKI 785
vandetanib
carboxypeptidase inhibitor from potato (PCI) protein
sprouty protein
Argos protein
lefty protein
IMC-C225

 

[Smooth]

people like myself, who doesnt understand a thing on whats going on this thread and would like to help with whatever, woudlnt know even from where to start.. so if your serius with tthat request of yours, be kind enough to link us to some "begginers" material so we can try to help out with searching...tc

 

[michael barry]

getfitinib is almost certainly the drug they will try to use. Its associated with weird hypertrichotic effects in a couple of clinical cases.



Down this thread, you can see a weird pic of terminal hair growing on someone's nose with getfitinib usage:
http://www.hairsite.com/hair-loss/board ... 33746.html

Third post down by TAGOHL......



If you follow this thread about a third to half of the way down, you will see a picture of strange hairgrowth in the middle of a bald man's scalp with usage of getfitinib for cancer (he died eventually of the cancer),
http://www.hairsite.com/hair-loss/board ... 33746.html


Notice how dark the hair is? While the rest of his hair is starting to grey--greying?




Getfitinib is extremely expensive---$2400 for 30 pills and about 1 in 100 users have a very bad side effect---scarring of thier lungs, which can end up being fatal after a while. The bad thing is, if you get the side effect............your lungs might start scarring within a day of beginning getfitinib. Smokers and those who are "underweight" and Asians are the most oft-effected by this. They are probably working on a topical formulation of this drug in my opinion that doesn't get internally absorbed, but still inhibits epidermal growth factor at the receptor by blocking certain tyrosine kineases there. Follica is now recruiting for a trial at Harvard with wounding only on bald scalp----probably to see what pathways are activated in response to wounding so they know what pathways need to be "activated" by other means to get hair in vivo, etc. That is a very positive development.
They will probably need this drug topically to make the process of epidermal stem cells building new hair follicles instead of more skin in response to a wound though.............................its going to be tested by them at Harvard now though, and this means the ball is really beginning to roll in the research process which is very good news.

 

[chancer]

getfitinib is almost certainly the drug they will try to use. Its associated with weird hypertrichotic effects in a couple of clinical cases.



Down this thread, you can see a weird pic of terminal hair growing on someone's nose with getfitinib usage:
http://www.hairsite.com/hair-loss/board ... 33746.html

Third post down by TAGOHL......



If you follow this thread about a third to half of the way down, you will see a picture of strange hairgrowth in the middle of a bald man's scalp with usage of getfitinib for cancer (he died eventually of the cancer),
http://www.hairsite.com/hair-loss/board ... 33746.html


Notice how dark the hair is? While the rest of his hair is starting to grey--greying?




Getfitinib is extremely expensive---$2400 for 30 pills and about 1 in 100 users have a very bad side effect---scarring of thier lungs, which can end up being fatal after a while. The bad thing is, if you get the side effect............your lungs might start scarring within a day of beginning getfitinib. Smokers and those who are "underweight" and Asians are the most oft-effected by this. They are probably working on a topical formulation of this drug in my opinion that doesn't get internally absorbed, but still inhibits epidermal growth factor at the receptor by blocking certain tyrosine kineases there. Follica is now recruiting for a trial at Harvard with wounding only on bald scalp----probably to see what pathways are activated in response to wounding so they know what pathways need to be "activated" by other means to get hair in vivo, etc. That is a very positive development.
They will probably need this drug topically to make the process of epidermal stem cells building new hair follicles instead of more skin in response to a wound though.............................its going to be tested by them at Harvard now though, and this means the ball is really beginning to roll in the research process which is very good news.

Speculation on my part... if they was to make a topical of Getfitinib, wouldn’t that have to go through the vigorous and lengthy testing of the FDA? I know the drug administered internally was given the ok by the FDA as a last resort to cancer sufferers, but if they wanted to do it topically and commercially then wouldn’t that throw it back like 5 yrs of testing?

 

[Matt27]

getfitinib is almost certainly the drug they will try to use. Its associated with weird hypertrichotic effects in a couple of clinical cases.



Down this thread, you can see a weird pic of terminal hair growing on someone's nose with getfitinib usage:
http://www.hairsite.com/hair-loss/board ... 33746.html

Third post down by TAGOHL......



If you follow this thread about a third to half of the way down, you will see a picture of strange hairgrowth in the middle of a bald man's scalp with usage of getfitinib for cancer (he died eventually of the cancer),
http://www.hairsite.com/hair-loss/board ... 33746.html


Notice how dark the hair is? While the rest of his hair is starting to grey--greying?




Getfitinib is extremely expensive---$2400 for 30 pills and about 1 in 100 users have a very bad side effect---scarring of thier lungs, which can end up being fatal after a while. The bad thing is, if you get the side effect............your lungs might start scarring within a day of beginning getfitinib. Smokers and those who are "underweight" and Asians are the most oft-effected by this. They are probably working on a topical formulation of this drug in my opinion that doesn't get internally absorbed, but still inhibits epidermal growth factor at the receptor by blocking certain tyrosine kineases there. Follica is now recruiting for a trial at Harvard with wounding only on bald scalp----probably to see what pathways are activated in response to wounding so they know what pathways need to be "activated" by other means to get hair in vivo, etc. That is a very positive development.
They will probably need this drug topically to make the process of epidermal stem cells building new hair follicles instead of more skin in response to a wound though.............................its going to be tested by them at Harvard now though, and this means the ball is really beginning to roll in the research process which is very good news.

Speculation on my part... if they was to make a topical of Getfitinib, wouldn’t that have to go through the vigorous and lengthy testing of the FDA? I know the drug administered internally was given the ok by the FDA as a last resort to cancer sufferers, but if they wanted to do it topically and commercially then wouldn’t that throw it back like 5 yrs of testing?

It would fall under off-label use, where a doctor can basically make up his or her own mind to use whatever drug(s) they have available to them to treat whatever ailment they see fit. This applies to any and all drugs that are FDA approved for *anything.* Now if the makers of Getfitinib wanted to legally sell their drug as a topical for hairloss then yes, they would have to go through years of trials and testing for safety and efficiency etc. in order to do that.

A doctor can basically grab any medicine off the shelf they want once it's FDA approved for something, it's up to their discretion. That's why you had some progressive/liberal docs prescribing Proscar for hairloss years before it went through clinical trials for it.

 

[Moomin]

Firstly off the top of my head Geinstein is also an EGFR inhibitor

Thanks for your info First, just out of interest did you consider that the the high absorption rate of lithium chloride (as oppose to orotate) may not need as extreme a penetrating solvent as DMSO, so ethanol might be a good alternative (and much safer). I suppose this depends on whether you're using DMSO for its properties as a solvent only or whether you believe it confers other advantages; I've heard it might have an affect on beta-catenin binding/production.

Also, chancer why does Follica's start of dermabrasion trials suggest a backward step. If depiliation and dermabrasion are the first steps in the follica method then why would they begin testing anything else first. I assume they will want to see what level of wounding will be required to initiate stem cell differentiation into hair follicles. When they have discovered this I believe they will try to determine what products are ideal for over expressing Wnt pathways; and perhaps, but not neccesarily they may try to augment any results achieved by over expressing Wnt by adding an EGFR inhibitor.

Imagine if after this first trial we were to find out that neo genesis in human skin, post wounding ,was a reality, which I have no doubt it will be. Then surely its just a question of time before unk:

This is not and should not be a pessimistic forum.

 

[first]

getfitinib is almost certainly the drug they will try to use. Its associated with weird hypertrichotic effects in a couple of clinical cases.



Down this thread, you can see a weird pic of terminal hair growing on someone's nose with getfitinib usage:
http://www.hairsite.com/hair-loss/board ... 33746.html

Third post down by TAGOHL......



If you follow this thread about a third to half of the way down, you will see a picture of strange hairgrowth in the middle of a bald man's scalp with usage of getfitinib for cancer (he died eventually of the cancer),
http://www.hairsite.com/hair-loss/board ... 33746.html


Notice how dark the hair is? While the rest of his hair is starting to grey--greying?

One thing that worries me a bit is that on both of those pictures it looks like it was body hair that was growing instead of real terminal scalp hair.