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Hair raising breakthrough in genetic engineering


#1

Well, not exactly hair raising but certainly jaw dropping. This new technique promises to revolutionise genetic engineering - which in turn, will eventually have a profound effect on inherited conditions such as baldness.

PS. I have been visiting this forum for many years now, and am troubled by the fact that at least half the discussions these days involve Dr Nigam and his trials and tribulations. Perhaps it is time to move on to other developments.


#2

This is a huge discovery. Since baldness is hereditary, and Cots has ties with Harvard, maybe he can work with these researches and come up with something. This is how baldness will be cured!


#3

[quote][postedby]Originally Posted by superhl[/postedby]
This is a huge discovery. Since baldness is hereditary, and Cots has ties with Harvard, maybe he can work with these researches and come up with something. This is how baldness will be cured![/quote]

This is great, but I’m still unsure as to what the delivery mechanism would be. In other words, how would they change the genes in all the hair follicle cells of your scalp at once? If they inject something into the skin, how would it propagate to all the cells?

This article says they would not be using modified viruses as a delivery vehicle, which is the normal delivery method used in gene therapy. Then what method would they use?

It seems that this idea is mainly useful for changing the DNA in sperm or egg, to prevent a baby from being born with a certain disorder, such as MPB. This is germline gene therapy, not adult somatic gene therapy.

I don’t see how this could be used to change the DNA in an adult human, such that you can target and impregnate only certain cells with the proper DNA sequence.


#4

[quote][postedby]Originally Posted by superhl[/postedby]
This is a huge discovery. Since baldness is hereditary, and Cots has ties with Harvard, maybe he can work with these researches and come up with something. This is how baldness will be cured!

[postedby]Originally Posted by roger_that[/postedby]

This is great, but I’m still unsure as to what the delivery mechanism would be. In other words, how would they change the genes in all the hair follicle cells of your scalp at once? If they inject something into the skin, how would it propagate to all the cells?

This article says they would not be using modified viruses as a delivery vehicle, which is the normal delivery method used in gene therapy. Then what method would they use?

It seems that this idea is mainly useful for changing the DNA in sperm or egg, to prevent a baby from being born with a certain disorder, such as MPB. This is germline gene therapy, not adult somatic gene therapy.

I don’t see how this could be used to change the DNA in an adult human, such that you can target and impregnate only certain cells with the proper DNA sequence.[/quote]

rodger_that, perhaps using similar methods that have been proposed for RNAi delivery (see: http://rnaitherapeutics.blogspot.co.uk/2012/05/skin-rnai-delivery-advancement-by.html , which would theoretically require repeated application for RNAi, but only once for CRISPR).

I think this is promising in a lab setting to probe gene function, but some time away from clinical application - for one reason in particular: off-target effects (See: http://www.nature.com/nbt/journal/v31/n9/abs/nbt.2623.html ).


#5

Germline manipulation is not exactly a reasonable method of treating MPB in my opinion.

We need to find a feasible way to fix this problem in the living. We don’t need to start screwing with the fabric of our future species just because the balding public is getting impatient. IMO mankind still hasn’t even made a decent effort against treating MPB in less radical ways. There are a few scattered researchers working very hard but most of the medical community acts like the problem is hardly worth attention.

Right now we don’t even understand sh*t about the biological implications of screwing with various genes, let alone the moral implications. We are decades away from the former and generations away from the latter.


#6

Although I’m skeptical this would be of any use to us baldies in our lifetime, I imagine it would be done the same way as current methods - in vitro.

A dermal sheath cup cell is isolated. Prior to being cultured, the gene is inserted into the DNA by a vector. Thereafter, each copy of the cell that replicates in the hanging drop culture contains a copy of the gene.

The bigger issue is that the gene/s for baldness itself have not definitively been identified.

If at all this gene therapy ends up being useful to us, it would be in the realm of halting the process of hairloss before it begins - a kind of vaccination against baldness. I doubt if it would be useful in helping bald guys get their hair back however - a much harder task.

Also it would be a million years before something like this gets through the FDA wall of bureaucracy.


#7

I don’t think it is realistic to expect to find just one or a few certain genes that cause MPB and nothing else good. Odds are that it’s the result of numerous genes which will turn out to interact in ways we aren’t near understanding yet. We may figure out that we can turn off MPB but it won’t be the same genes in everyone who has it and some of them aren’t options to mess with for ones reason or another.

I have no faith in treating MPB with genetic work. This is just not that kind of problem. Its a cosmetic skin issue. It just needs a treatment option that isn’t a total joke. It should be surmountable with existing science if there was a serious effort to do it. IMHO we have not seen a serious effort on the part of medical science yet. Science is still way more interested in preserving all life than improving anyone’s quality-of-life.


#8

this will only be applicable for organisms starting from a single cell.
never the less, this is great news.


#9

[quote][postedby]Originally Posted by The_Real_NW2[/postedby]
this will only be applicable for organisms starting from a single cell.
never the less, this is great news.[/quote]

Not necessarily true, The_Real_NW2.


#10

" Its a cosmetic skin issue. It just needs a treatment option that isn’t a total joke. It should be surmountable with existing science if there was a serious effort to do it. IMHO we have not seen a serious effort on the part of medical science yet. Science is still way more interested in preserving all life than improving anyone’s quality-of-life. "

cal, you have been visiting these forums for too much time, you need a rest


#11

Actually I haven’t been around as much lately. The swordfighting over Dr. Nigam bores me to death.

My comment about the medical community’s neglecting quality-of-life issues is a longstanding opinion. That dates back to before I was even dealing with MPB.


#12

DNA editing has been around for quite some time. Look for example at www.sangamo.com who is using Zinc finger technology to obtain the same goal. They’re in Phase II with both a trial for HIV and for Alzheimer (with great results so far). Supposedly this new technology is a bit easier to use but ZFN technology is exactly as precise.

I doubt this will be of use for baldies though. ZFN technology is super expensive, I think it costs about 100k to treat a HIV patient. Supposedly this new technology is cheaper but still, it would be very costly. And AFAIK the fundamental knowledge of which DNA to change lacks too. Besides it could only work as a preventive measure.

Also, we’re very close to solving the hairloss puzzle already. I would be amazed if there’s no cure in 10 years. So why would a company invest all that money into a hairloss therapy while there are tons of other diseases that are much farther away from a cure.


#13

[quote]
Also, we’re very close to solving the hairloss puzzle already. I would be amazed if there’s no cure in 10 years. So why would a company invest all that money into a hairloss therapy while there are tons of other diseases that are much farther away from a cure.[/quote]

Who is so close?

Not Aderans, Histogen, Replicel, Dr. Nigam, or Cots/Follica.

None of them have even demonstrated anything especially stronger than Fin/Minox so far, let alone any kind of game-changing treatment that makes MPB a problem of the past. It’s still nothing but hopes and possibilities at the end of 2013.


#14

Jahoda and Christiano seem to be closest to a fundamental solution now.


#15

[quote]
Also, we’re very close to solving the hairloss puzzle already. I would be amazed if there’s no cure in 10 years. So why would a company invest all that money into a hairloss therapy while there are tons of other diseases that are much farther away from a cure.

[postedby]Originally Posted by cal[/postedby]

Who is so close?

Not Aderans, Histogen, Replicel, Dr. Nigam, or Cots/Follica.

None of them have even demonstrated anything especially stronger than Fin/Minox so far, let alone any kind of game-changing treatment that makes MPB a problem of the past. It’s still nothing but hopes and possibilities at the end of 2013.[/quote]

Nope, none of the mentioned above, they’re all a bunch of losers, lol. But Jahoda and his buddies really are close. Same goes for Tsuji labs. And then a bunch Chinese lead by dr “Li” are also on their level. They all, independently, succeeded at generating follicles already.


#16

The paper “Future Horizons in Hair Restoration” that was recently published by dr Washenik (from Aderans) sums it up:

Recently, a big breakthrough was made by Li and colleagues, who created human follicles from cultured dermal and epidermal cells in a nu/nu mouse model. In their initial work, TSC2 null fibroblasts were combined with foreskin keratinocytes in a skin construct model. Once a nascent epidermal basal layer was formed in vitro, the skin construct was grafted on the back of a nu/nu mouse. The continued development of the skin resulted in the formation of hair follicles and sebaceous glands. This work represents the first published account of the formation of human hair from cultured cells.”

(He then talks about Jahoda’s group, including dr Higgins) ->

“In a separate system, Higgins and colleagues reported the formation of human hair using DP cells cultured as spheroids and combined with the epidermis of an excised human foreskin in a sandwich assay. For the first time, cultured human cells were used to form a completely human hair follicle. The expansion of these techniques provides a potentially unlimited supply of hair for the treatment of alopecia.”

“Recently, Toyoshima and colleagues (Tsuji Lab) created a bioengineered hair follicle germ using embryonic skin-derived epithelium and mesenchymal donor cells. The transplanted germ integrated with the host epithelium, producing a fully functional hair follicle demonstrating connection to the host nerves as well as to the piloerection ability. They further demonstrated that through the use of a guide, the interaction between these donor cells and the host epithelium was independent of placement depth. Taken together, these studies demonstrate that cells delivered in the appropriate package are able to integrate with the host tissue to produce a hair follicle. This technique would provide the clinician the ability to control the pattern, density, and orientation of the follicles resulting from this cell-based therapy.”

“A revolutionary breakthrough in the field of cell biology was the discovery of induced pluripotent stem cells (iPSCs). The work by Takahashi and colleagues described the ability of 4 transcription factors (SOX2, OCT4, c-MYC, and KLF-4) to reprogram differentiated fibroblasts into an embryonic stem cell state. From these cells, the creation of every lineage is possible.”

“Bilousova and colleagues have exploited this process to produce a multipotent keratinocyte lineage from mouse iPSCs. Retinoic acid, BMP4, and a collagen IV substrate were used to push the fate of the iPSCs to a keratinocyte lineage. The keratinocytes produced by this method demonstrated the ability to form skin and all of its appendages including the hair follicle. Itoh and colleagues used similar methods to generate human keratinocytes from iPSCs and produced 3-dimensional skin equivalents.
In this human model, appendages were not produced, but the foundation of reprogramming iPSCs into keratinocytes was established. iPSCs represent an unlimited supply of cells for each patient. The potential will be unlocked as research groups develop methods to differentiate iPSCs into follicular progenitor cells.”

He ends his paper with the following which is very positive

Recent developments in the field of regenerative medicine indicate that a cell-based solution for alopecia is coming soon. Multiple groups have produced human hair follicles using cultured cells in a mouse model. Strategies are being developed to expand and maintain trichogenic cells in culture. iPS cells provide an additional strategy to obtain follicular progenitor cells. The challenge is to exploit these methods and determine the most efficient and efficacious method of culture, expansion, and delivery of follicular progenitor cells.”

We’re close, man. Of course not 1-2 years but I’d be really amazed if there would be no real cure available in 8 years from now. These recent breakthroughs are undeniably HUGE.


#17

[quote]
We’re close, man. Of course not 1-2 years but I’d be really amazed if there would be no real cure available in… [/quote]

Aren’t we always just 5 years away from the cure…


#18

[quote]
We’re close, man. Of course not 1-2 years but I’d be really amazed if there would be no real cure available in…

[postedby]Originally Posted by Freddie555[/postedby]

Aren’t we always just 5 years away from the cure…[/quote]

You see comments like this on the boards. It’s understandable. People put all of their hopes in for example a Dr Nigam and when it turns out he didnt have anything other than some photoshopped pictures, they give up all hope and think we’ll never get there. They don’t understand science nor can they interpret current milestones. Cause if they did and they did read those quotes from that article that I just posted, people wouldn’t dare to say that.

Really, come on man. Several independent research groups have succeeded already at generating grafts from cells !! This is something we didnt even dare to dream of 5 years ago and now it’s reality. Not just 1 researcher. Several independent research groups did it !! Forget about dr Nigam, read up on the real scientists and you’ll get hope again. They’re so close !!


#19

In medicine being close in a lab, still means being very very far away from the end-consumer market.

They aren’t yet even able to cosmetically viable hair consistently in large amounts in a lab. Once they can do that (which take years) they need to go through FDA. I think we are still looking at a decade.

[quote]
We’re close, man. Of course not 1-2 years but I’d be really amazed if there would be no real cure available in…

[postedby]Originally Posted by Freddie555[/postedby]

Aren’t we always just 5 years away from the cure…

[postedby]Originally Posted by Lindo[/postedby]

You see comments like this on the boards. It’s understandable. People put all of their hopes in for example a Dr Nigam and when it turns out he didnt have anything other than some photoshopped pictures, they give up all hope and think we’ll never get there. They don’t understand science nor can they interpret current milestones. Cause if they did and they did read those quotes from that article that I just posted, people wouldn’t dare to say that.

Really, come on man. Several independent research groups have succeeded already at generating grafts from cells !! This is something we didnt even dare to dream of 5 years ago and now it’s reality. Not just 1 researcher. Several independent research groups did it !! Forget about dr Nigam, read up on the real scientists and you’ll get hope again. They’re so close !![/quote]


#20

[quote]In medicine being close in a lab, still means being very very far away from the end-consumer market.

They aren’t yet even able to cosmetically viable hair consistently in large amounts in a lab. Once they can do that (which take years) they need to go through FDA. I think we are still looking at a decade.

We’re close, man. Of course not 1-2 years but I’d be really amazed if there would be no real cure available in…

[postedby]Originally Posted by Freddie555[/postedby]

Aren’t we always just 5 years away from the cure…

[postedby]Originally Posted by Lindo[/postedby]

You see comments like this on the boards. It’s understandable. People put all of their hopes in for example a Dr Nigam and when it turns out he didnt have anything other than some photoshopped pictures, they give up all hope and think we’ll never get there. They don’t understand science nor can they interpret current milestones. Cause if they did and they did read those quotes from that article that I just posted, people wouldn’t dare to say that.

Really, come on man. Several independent research groups have succeeded already at generating grafts from cells !! This is something we didnt even dare to dream of 5 years ago and now it’s reality. Not just 1 researcher. Several independent research groups did it !! Forget about dr Nigam, read up on the real scientists and you’ll get hope again. They’re so close !!

[postedby]Originally Posted by hairman2[/postedby][/quote]

Yup, we’re looking at 8-10 years. Guys like Freddy will say “but it always will be a decade”. But they ignore current milestones and recent breakthroughs. At this point is just about optimizing the process, figuring out the intrinisic hair properties and testing safety in human trials, which might start in 1-2 years already. (Tsuji lab said 3 years a year ago and Jahoda’s group said they felt confident to start ‘soon’ too).