Application Of Crispr To Androgenic Alopecia.

[Beowulf]

CRISPR gene-editing tested in a person for the first time
http://www.nature.com/news/crispr-gene-editing-tested-in-a-person-for-the-first-time-1.20988

The rise of CRISPR is certainly exciting, however at this stage we should probably consider just how applicable it is to our circumstances.

Long story short, yes Androgenetic Alopecia is certainly a genetic illness, and CRISPR can indeed fix our genome.

However so far (from what I understand) CRISPR is only being used in vitro (probably because they do not think that it is accurate enough for use in vivo).

At the moment it does look like one way to use CRISPR is to completely knock out the Androgen Receptor gene in all the cells of the scalp. That way just about all the hair you have, and ever will have will be completely immune to the effects of DHT.

But we have to consider the vector. The cas9 and sgRNA need a way to reach the DNA that it is going to knock out.

One option is adeno-associated viruses. This seems pretty standard practice in the field. According to InBeforeTheCure they can be changed in order to only effect a particular cell type. In our case it seems that we would need to target both the epithelial stem cells in the bulge (to protect future hair follicles) and the dermal papilla cells in the dermal papilla (to keep what you've got).

This form of treatment is actually pretty cheap, so there's no reason why you couldn't make one for each stem cell type. The only problem I have with it is that I don't know how specific you can make AAV's, considering that we still want AR's in the rest of our bodies.

https://www.addgene.org/61591/

Another option seems to be liposomes. As Gone pointed out though most studies are quite vague about the effectiveness of liposomes because they don't differentiate between the hair follicle dermal papilla cells or the epithelial cells. In any case Hoffman (2006) seems to think that liposomes were very efficacious and safe to use with gene therapy.

https://www.ncbi.nlm.nih.gov/m/pubmed/9588863/?i=6&from=/11399544/related

For all I know at this point you might be able to target the dermal papilla with the liposomes and then get the epithelial with an AAV.

I'll probably come back a bit later to this, but what do you guys think?

 

[nameless]

I think that you want to be 100% sure that it will only knock out the ARs in your scalp before you undergo such a treatment. If you knock out ARs in other parts of your body that will be FAR more upsetting than hair loss. I think our best hope is Tsuji. Dr. Tsuji's technology will likely not come to market for another few years but I'm 99.9% sure it will finally cure hair loss.

Replicel/Shiseido is similar to Dr. Tsuji's technology but Tsuji's technology is superior. I do not expect Replicel/Shiseido will work. I think that we now see Shiseido and Replicel bickering because at least one of these two companies realizes that the technology is insufficient to cure hair loss.

Put your faith in Dr. Tsuji because his technology is the most certain.

And start saving money because you will need money in 2020. Figure travel expenses to and from Asia 2 or 3 times plus accommodations, transportation and food while you're there. And then there's the cost of treatment. I anticipate the cost of treatment will be $20,000 US to $50,000.

 

[Beowulf]

I think that you want to be 100% sure that it will only knock out the ARs in your scalp before you undergo such a treatment. If you knock out ARs in other parts of your body that will be FAR more upsetting than hair loss. I think our best hope is Tsuji. Dr. Tsuji will likely not come to market for another few years but I'm 99.9% sure it will finally cure hair loss.

Replicel/Shiseido is similar to Dr. Tsuji's technology but Tsuji's technology is superior. I do not expect Replicel/Shiseido will work. I think that The two companies are doing some bickering now because at least one of them knows that the technology is insufficient to cure hair loss. Put your faith in Dr. Tsuji because his technology is the most certain.

And start saving money because you will need money in 2020. Figure travel expenses to and from Asia 2 or 3 times plus accommodations, transportation and food while your there. And then there's the cost of treatment. I anticipate the cost of treatment will be $20,000 US to $50,000.

I'm sure Tsuji's treatment will work, but it's not really a cure. CRISPR would actually be a cure, it would completely remove the possibility of Androgenetic Alopecia. It would be cheap, effective and convenient.

The thing with Tsuji is that yeah, it will be incredibly expensive, but you've also got to beat the thousands of wealthy Japanese people who will be lining up. They already said they only expect to do about 10,000 treatments in the first year, it might be a little while before any of us manage to get to the front of the queue.

The only real problem with CRISPR is getting through trials, but even then the problem is more safety than efficacy, and for all we know the FDA might loosen up a bit.

With the AAV's I only know that they can target specific cell types such as adipose, which means that the only potential side effects are inability to produce acne, softer, younger skin, and the retardation of new beard growth. But my fear is that it would not target the dermal papilla which is made up of stem cells. If they could be adapted so they only effected the dermal papilla cells then it would be perfect.

In the liposome case the most likely side effect is to get rid of the androgen receptors in the face, but assuming the liposome doesn't break down it probably wouldn't be very many.

 

[plisk]

I wouldnt bother getting yourself hyped up about CRISPR. Its a pipe dream that is being hyped up so these startups can get investors dicks hard for that research moola.

Put it this way, by the time you can 'cure' male pattern baldness with CRISPR technology, male pattern baldness will probably not be high on your priority list lol

 

[That Guy]

I'm sure Tsuji's treatment will work, but it's not really a cure. CRISPR would actually be a cure, it would completely remove the possibility of Androgenetic Alopecia. It would be cheap, effective and convenient.

A cure is anything that relieves you of the symptoms and effects of the disease; that is the literal definition.

Beowulf, broseph...you're making a basic logic error here. If Tsuji's treatment, despite giving you (as anticipated) a lasting, full head of hair is not a cure, but genetic engineering does because it removes the possibility of getting it altogether, then you must accept that following this logic, anyone who is already alive and balding can never be cured.

What if you were NW3, got CRISPR'd and then Tsuji'd to replace the lost hair? Would you only be like 75% cured?

I wouldnt bother getting yourself hyped up about CRISPR. Its a pipe dream that is being hyped up so these startups can get investors dicks hard for that research moola.

Put it this way, by the time you can 'cure' male pattern baldness with CRISPR technology, male pattern baldness will probably not be high on your priority list lol

I really must disagree with the first part of your post. There is just about nothing else out there right now that has real potential to change the world forever. Very few scientists aren't excited about CRISPR. Just have to wait and see the results from these trials.

I do agree with your second point, though. It appears that it will be decades before gene editing is put into widespread use for a myriad of problems. The people who will benefit the most from gene editing have not been born yet.

 

[Folliman]

Yes, it will be possible, but I wouldn't count on it. It's so early in development and researchers are going to first focus on cancer.

 

[Grasshüpfer]

Only crispr is precise and therefore safe enough to use in humans, but can't be targeted to specific cells.

And the adeno-associated viruses are too dangerous to use in humans. They are not precise, which means that they also edit unwanted genes sometimes. Like doing surgery with a shotgun. But they could be targeted only to cells in the scalp.

So we are not there yet.

- Still we are now in the age of gene editing in human cancer therapy, which was deemed possible around 2100 ten years ago.

 

[Folliman]

I meant they're going to use it to research cancer cells first

 

[Grasshüpfer]

Maybe to clarify the news i posted..

What they did is:

1. Take immune system cells from a patient.
2. Upgrade them using crispr, so they can see cancer cells, which were invisible to the immune system before.
3. Insert the cells back into the patient and let them attack the cancer.

 

[Beowulf]

Beowulf, broseph...you're making a basic logic error here. If Tsuji's treatment, despite giving you (as anticipated) a lasting, full head of hair is not a cure, but genetic engineering does because it removes the possibility of getting it altogether, then you must accept that following this logic, anyone who is already alive and balding can never be cured.

Sorry but I only made this thread because I want to consider the ramifications of CRISPR for genetic hairloss without further shiting up the GWAS thread. I shouldn't have argued in the first place, my bad. (Plus I spent all of last semester studying what makes mental diseases diseases and I'd rather take a break for a while!)

Only crispr is precise and therefore safe enough to use in humans, but can't be targeted to specific cells.

And the adeno-associated viruses are too dangerous to use in humans. They are not precise, which means that they also edit unwanted genes sometimes. Like doing surgery with a shotgun. But they could be targeted only to cells in the scalp.

Sorry I'm a little bit confused about this point, from what I understand CRISPR is still too dangerous to use in humans because it still leads to downstream cuts, that's why they're starting with cancer because all they need to do is change the T-cells in vitro where they can check for off target cuts before putting them back in.


I've read a few articles such as
Engineering targeted viral vectors for gene therapy by Reinhard Waehler, Stephen J. Russell and David T. Curiel and Receptor targeting of adeno-associated virus vectors and I'm way over my head. From what I can tell none of them seem to focus on making sure that it only goes to a specific type of cell, but rather that it gets to the target cell. Some of them seem to think that if you just stick it in the tissue it will just stay there.


InBeforeTheCure mentioned some stuff about how you could make it selective active with a particular chemical, then it would be a one time lotion. The good news is that it doesn't seem like any of this stuff can actually get past the blood brain barrier, so we're safe on that front. It's just stopping it from getting into the testes. But then again a liposome might take care of that anyway.

 

[InBeforeTheCure]

InBeforeTheCure mentioned some stuff about how you could make it selective active with a particular chemical, then it would be a one time lotion.

No, you would have to keep using it just as you have to keep using any other topical. Transcription of the siRNA would depend on presence of the chemical, so it would be turned on when the chemical is present off when it isn't.

 

[Grasshüpfer]

(...), so it would be turned on when the chemical is present off when it isn't.

Which is a good thing so if you happen to get brain fog, you re not permanently dumb.

Btw @Beowulf, we had a discussion somewhere about crispr and I can't find it for my life. I think in the end you were right. We are both broscientists with a lot of isolated knowledge.
It's fun to be proven wrong and learn and I really appreciate your posts.

 

[RatherGoBlindThanSeeItGo]

Seems to me like male pattern baldness is mostly genetic so I don't see why CRISPR shouldn't be able to edit specific genes provided we are able to locate the genes and understand the process that leads to male pattern baldness, which we currently don't. It really sounds like pie in the sky for now but I wonder about if/when they will be able to do so, whether that would reverse male pattern baldness or whether the damage is mostly permanent. I think it's probably the latter so it's probably nothing to get our hopes up about, even among the youngest of us.

 

[Grasshüpfer]

@RatherGoBlindThanSeeItGo

Quite straight analysis, but I think you are right. Then again the further we push into sci fi territory here the more I believe in Tsuji.

 

[Folliman]

Maybe to clarify the news i posted..

What they did is:

1. Take immune system cells from a patient.
2. Upgrade them using crispr, so they can see cancer cells, which were invisible to the immune system before.
3. Insert the cells back into the patient and let them attack the cancer.

Sorry man, I'm guilty of not having read the article before commenting, I thought they were still testing this in vitro. This is a very important step for medicine indeed. Very exciting news!

 

[Beowulf]

Which is a good thing so if you happen to get brain fog, you re not permanently dumb.

Btw @Beowulf, we had a discussion somewhere about crispr and I can't find it for my life. I think in the end you were right. We are both broscientists with a lot of isolated knowledge.
It's fun to be proven wrong and learn and I really appreciate your posts.

I feel the same way. I'd be pretty lost without guys like you, InBeforeTheCure, Swoop, Armando and Co. It's really nice how we all come together to find a solution to our problem!

 

[Trouse]

I feel the same way. I'd be pretty lost without guys like you, InBeforeTheCure, Swoop, Armando and Co. It's really nice how we all come together to find a solution to our problem!

Wait.....so you've found a solution to balding and you've been holding out on us this whole time?

 

[Beowulf]

Wait.....so you've found a solution to balding and you've been holding out on us this whole time?

You got me, it's sea otter blood.