Reason why there is still no cure in 2013 and the solution

[Dan26]

I think BMP signalling is key Desmond...a piece of the puzzle, amongst other things

http://genesdev.cshlp.org/content/22/4/543.long

Hair follicle (HF) formation is initiated when epithelial stem cells receive cues from specialized mesenchymal dermal papilla (DP) cells. In culture, DP cells lose their HF-inducing properties, but during hair growth in vivo, they reside within the HF bulb and instruct surrounding epithelial progenitors to orchestrate the complex hair differentiation program. To gain insights into the molecular program that maintains DP cell fate, we previously purified DP cells and four neighboring populations and defined their cell-type-specific molecular signatures. Here, we exploit this information to show that the bulb microenvironment is rich in bone morphogenetic proteins (BMPs) that act on DP cells to maintain key signature features in vitro and hair-inducing activity in vivo. By employing a novel in vitro/in vivo hybrid knockout assay, we ablate BMP receptor 1a in purified DP cells. When DPs cannot receive BMP signals, they lose signature characteristics in vitro and fail to generate HFs when engrafted with epithelial stem cells in vivo. These results reveal that BMP signaling, in addition to its key role in epithelial stem cell maintenance and progenitor cell differentiation, is essential for DP cell function, and suggest that it is a critical feature of the complex epithelial–mesenchymal cross-talk necessary to make hair.

[Dan26]

ahh i just read the previous posts...

wnt, bmp, fgf

looking at the dates of some of these studies is sad...your right desmond in that the respective teams of researchers need to be well aware of each others work! Things move to damn slow

[idontwant2bebalding]

http://www.nature.com/jid/journal/v133/n11/full/jid2013322a.html

The field of skin biology is beautifully dynamic and growing rapidly. This expanding wave of new knowledge is transforming the clinical practice of dermatology on a constant basis. Key to translating the new knowledge being acquired about skin disease is the conduit of skills and knowledge that can reliably move such discoveries through the maze of activities needed to bring change to clinical practice. There are many links in this chain. We must maintain a diverse physician–scientist workforce that can conduct basic and clinical research and serve as teaching faculty in departments of dermatology. Researchers with broad expertise in basic, translational, and clinical research are also needed for the field to thrive. To achieve success in moving knowledge from the bench to the bedside, individuals are needed both in departments of dermatology and other university departments and in private enterprise conducting skin-related research and product development.

Someone should reach out to this group and suggest that we can help.

[Desmond84]

I think BMP signalling is key Desmond...a piece of the puzzle, amongst other things

http://genesdev.cshlp.org/content/22/4/543.long

Hair follicle (HF) formation is initiated when epithelial stem cells receive cues from specialized mesenchymal dermal papilla (DP) cells. In culture, DP cells lose their HF-inducing properties, but during hair growth in vivo, they reside within the HF bulb and instruct surrounding epithelial progenitors to orchestrate the complex hair differentiation program. To gain insights into the molecular program that maintains DP cell fate, we previously purified DP cells and four neighboring populations and defined their cell-type-specific molecular signatures. Here, we exploit this information to show that the bulb microenvironment is rich in bone morphogenetic proteins (BMPs) that act on DP cells to maintain key signature features in vitro and hair-inducing activity in vivo. By employing a novel in vitro/in vivo hybrid knockout assay, we ablate BMP receptor 1a in purified DP cells. When DPs cannot receive BMP signals, they lose signature characteristics in vitro and fail to generate HFs when engrafted with epithelial stem cells in vivo. These results reveal that BMP signaling, in addition to its key role in epithelial stem cell maintenance and progenitor cell differentiation, is essential for DP cell function, and suggest that it is a critical feature of the complex epithelial–mesenchymal cross-talk necessary to make hair.

Yeah Dan, I've read this paper actually

I don't know if you remember the post I made about the "first dermal signal". I have this gut feeling that the key to DP cell expansion lies within these signals! During embryogenesis the "first dermal signal" tells mesenchymal:epithelial cells that are in contact with each other to form DP cells! That's it! Unfortunately though, we only know less than a handful of these signals and most of them are unkown! The ones we know of are:

- BMP (activation)
- Wnt (inhibition & activation)
- FGF (inhibition)
- Vitamin D (promoter)

Dr Ohyama tested these signals and they significantly increased gene expression of cultured DP cells. This was only a year ago!

This is my 5 year plan:

First 2 years: Combine Ohyama's signals with Jahoda's 3D spheroid technique to master DP culturing expansion!

Next 3 years: Follow Tsuji's "Hair germ method" technology to generate human hair follicles by using these cultured DP cells and epithelial stem cells.

I'm seeing another Professor in Sydney on Wednesday to see if he's prepared to take me on! - Fingers crossed!

On a side note: guys imagine if we could have enough money to give researchers grants to conduct these studies. How awesome would that be?

[Desmond84]

looking at the dates of some of these studies is sad...your right desmond in that the respective teams of researchers need to be well aware of each others work! Things move to damn slow

Yeah dude...we really need to approach this in a very organised or collaborative manner or nothing conclusive will come of this research till 2030!

I was reading one of the life-extension blogs the other day and came across this post by a researcher in this field. It conveys my worries whole heartedly...(Note. he is talking about using 'regenerative medicine' technology to extend life but the jist of what he is saying is very relevant to bioengineering hair follicles):

"Cards on the table: the wrong side of 40 looms for some of us. The present regulatory systems for medical development in the US and most other regions contributing meaningfully to progress don't look likely to become any less oppressive in the years ahead. It presently takes ten to twenty years to move a good research result out of trials and into the clinics, and that time frame is largely based on organizational activities and regulatory make-work that won't be speeded up by ongoing advances in biotechnology. Furthermore, the regulatory environment destroys or prevents many beneficial development programs by making them unprofitable.

This means that present glimmers of medical technologies capable of repairing specific forms of biochemical damage, such as work on mitochondrial repair, will most likely not be available for general use until people like me are hitting 60. They won't ever be available for healthy people "aging normally" inside US borders absent a revolution in the way the FDA operates. The same goes for organ replacement, other forms of growing any new tissue you like to order, rebooting the immune system, and so on.

Here is today's speculation: will these technologies of 2030 be good enough to grant an additional 20 years of life? How much certainty will there be by that time that these technologies will extend life significantly in humans? These are not questions that can be answered with any degree of certainty - you can only speculate.

People of my generation are most likely not going to get two shots at this. If the technology of 2030 isn't up to the task, then we don't plausibly get to wait around to 2050 and age 80. The trouble with being 80 is that (a) many people don't in fact make it that far, even allowing for a continuing upward trend in life expectancy, and (b) you may no longer be robust enough to have a good chance of surviving early rejuvenation therapies. The clock is ticking.

I have said in the past that, from a pure research timeline perspective, by 2040 we'll plausibly have all the technologies needed to repair and reverse aging. Unfortunately when we look beyond the laboratory, the field is strewn with roadblocks of legislation, slowing everything down. Even the time taken for new businesses to raise capital, try, fail, and try again is less than the delays imposed by the ball and chain of regulation."

I really fear same would apply to a baldness cure if we don't do something!

[Desmond84]

My hopes lie with China.

China's recent interest in medical research is definitely a nice change in the atmosphere. Now that they've surpassed the number of USA PhD graduates, you can be more than certain they'll be working on some major medical breakthroughs in the coming years.

Furthermore, they lack the strict and diligent regulatory framework of FDA, TGA and EMEA allowing just about enough air for bio-start ups to breath in some fresh air and fly new heights!

[Desmond84]

Here's another interesting view of why biomedical technology will never be on an exponential rise compared to the explosion of Information technology we've witnessed in the last 3 decades.

Is FDA the problem?
By Juan Enríquez Cabot

(Excerpt from his talk at last year's investment symposium from Agora Financial.)

Today, it costs 100,000 times less than it once did to create a three-dimensional map of a disease-causing protein

There are about 300 times more of these disease proteins in databases now than in past times,

The number of drug-like chemicals per researcher has increased 800 times

The cost to test a drug versus a protein has decreased ten-fold

The technology to conduct these tests has gotten much quicker

Now here’s a simple question:

"Given all these advances, why haven’t we cured cancer yet? Why haven’t we cured Alzheimer’s? Why haven’t we cured Parkinson’s?"

The answer likely lies in the bloated process and downright hostile-to-innovation climate for FDA drug approvals in this day and age...

According to Enriquez, this climate has gotten so bad that major pharmaceuticals companies have begun shifting their primary focus from R&D of new drugs to increased marketing of existing drugs — and mergers and acquisitions.

Here's little bit about Juan Enríquez Cabot in case you were wondering who he is:

He was the founding director of the Life Sciences Project at Harvard Business School and a fellow at Harvard's Center for International Affairs.

His work has been published in Harvard Business Review, Foreign Policy, Science, and The New York Times. He is the author of Homo Evolutis, As the Future Catches You and The Untied States of America. He works in business, science, and domestic/international politics.

Juan Enríquez is recognized as one of the world's leading authorities on the economic and political impacts of life sciences. He is currently Chairman and CEO of Biotechonomy LLC, a life sciences research and investment firm.

[Desmond84]

I have to admit though I personally don't blame the FDA...we just don't have a better model to test drug safety atm...and that is on its way but it's at least 10 years away and maybe more. Once we can generate actual organs as drug models, Phase 1 and 2 will pretty much be irrelevant.

Till then, we really need to look at Asia for some help...Japan's already opening up the way for more easy-going approach towards the iPS cell research in humans which is great! Hopefully China will follow and we see some kind of breakthrough sooner than later

[Desmond84]

http://www.nature.com/jid/journal/v1...d2013322a.html

Someone should reach out to this group and suggest that we can help.

We need to have an organisation to communicate with them. They don't really see us as anything of value (sadly)...Academia need just as much of an overhaul as the FDA.

I've recently realised the number of hoops to get across for anyone in the academic world to take you seriously and provide you with a minute grant to undertake your research!

We really need this crowdfunding idea to start

[Tomb10]

I thought first that you where a member with high knowledge of the ''hair'' future.
But I have the idea that you only talk to your own mood. one moment is the cure almost reached "that we al get a nw1'' . and the next moment everything is sad, and it will take decades.
last week you give all your hope to japan, and now china is the big country in medical research...
There are many followers who take you seriously, but in this way you give many people a false impression of the situation.

[Desmond84]

I thought first that you where a member with high knowledge of the ''hair'' future.
But I have the idea that you only talk to your own mood. one moment is the cure almost reached "that we al get a nw1'' . and the next moment everything is sad, and it will take decades.
last week you give all your hope to japan, and now china is the big country in medical research...
There are many followers who take you seriously, but in this way you give many people a false impression of the situation.

Tomb, I think it's important to discuss all the avenues to a hairloss cure. We have many problems ahead. Some scientific, some regulatory and some financial.

The scientific breakthroughs seems to be happening in US and Japan, whereas the regulatory problems can be overcome by Asia (particularly China). Funding is a whole other problem. Unless we can prove to venture capitalists we have a solid treatment ready for human trials, most of them will simply not even give us a moment of consideration.

My posts today are mostly about the regulatory burden placed on smaller biotech companies in the western world that stops them from bringing out a given therapy. Histogen is a mere example that we've been following closely for the past 5 years. I'm more than certain engineering hair follicles would face even greater regulatory scrutiny in the US than your typical treatment due to its stem cell nature (particularly if we go down the iPS path).

But there is no doubt that the scientific work to bring about an actual cure is very solid. We are close and Jahoda knows it as well. As you said, we've discussed it already in this thread.

Next step is to bring about an environment where these scientists can test out their finding with sufficient funding in a laxed regulatory environment in a more research-friendly country...in order for a solution to be here by 2020. This step requires ppl of all fields to step up and lend a hand. We especially need ppl in the financial arena to give us tips on how to attract investors and ways to come up with more funding.

This thread was started to discuss the scientific shortcomings but I thought I should share some of the other problems we may be facing down the line as it is important to know and prepare then blindly step into the world of new challenges. I think most of us have learnt a whole lot watching Histogen jumping through hoops and can see the same happening to the next start-up company of our interest.

My aim is to open discussion, so when the time comes...we have thought things through. I'm serious about investing the next few years of my life to overcome this disease...and to do so need all your help and advice.

[brunobald]

We need to fund guys like Desmond, he wants to do the research, he has the ability but there is no funding.

When I was working at a consumer product company in the UK as a Design engineer, we employed a PHD student from MIT to work for a year on a particular research project we set him. For the years work I think it was around £30,000-£40,000. This would include all materials and the use of the university lab, plus help from tutors etc...

If we set up a lab to run a certain project it would cost £100,000's so by using the university we would make use of their lab and infastructure already in place.

If Desmond was willing maybe we could use him as the first crowdfunding project. See how many people we can get to chip in £5 or so for the first year of research.

[Arashi]

Yeah but Arashi, the trick is to know how to go from iPS cells to a specific cell line. Some we have figured out but most we are still puzzled on...DP cells being one of them.

iPS cells are definitely a new and radical approach to tackle this problem BUT we should also try the former as it may prove to be safer at least in the short run (as you stated )

The (bitter) irony here is that DP cells are currently being used as a source for the creation of iPS cells: " Here, we exploit that dermal papilla (DP) cells from hair follicles in the skin express all but one reprogramming factors to show that these accessible cells can be reprogrammed into iPS cells with the single transcription factor Oct4 and without further manipulation"

http://www.ncbi.nlm.nih.gov/pubmed/21563278

Then why is it so damn difficult to go the other way around ? And again, that's all we need, right ? DP + epethelial cells = follicle (as shown by Tsuji). iPS can nowadays be quickly and efficiently expanded. So the idea would be to get DP cells, transform them into iPS, expand and induce them to DP again and we can pop the champagne, right ? And the only part of that process that hasn't been done yet is that iPS -> DP part.

Tsuji showed us that the *human* hair they generated had all the same intrinisic properties (color, thickness etc) as the donor had. So really, it's only that step from iPS -> DP that's left.

[Arashi]

(or of course the Jahoda way and culture them, but then that has to be optimized to get to more gene expression)

[tonypizza]

The problem is everyone is focused on the researchers who are working on 2050 technology - body tissue regeneration. No one is working on 2013 technology - body form implants.

The technology for dental, joint, and heart valve implants has probably been in the works for hundreds of years. Only within the last hundred years has the technology and aseptic technique been sufficient to replace these lost tissues with artificial materials without rejection, and with function. Today, osseointegrated (dental) implants are the gold standard in terms of successful replacement of a lost tissue, and orthopedic surgeons will soon use the same technology in their fields. The material (titanium) is biocompatable, durable, hard, light, and cost-efficient. Plate and screw implant technology which replace joints still works fine, but is a good example of how over time technology becomes better and better, this being an old technology that was also used by dentists, but has recently been replaced by that field's researchers with a better technology which requires less surface area for integration with the bone, and incorporates the screw and functional appliance into one smaller unit.

Body tissue regeneration is being attempted in dentistry as well, and it is a massive mess. The technology isn't there. The understanding isn't there. The materials are unknown. It will be years before a working model is formed, and even then, it will be cumbersome and awkward, though it works. To grow a hair follice is the same principle as growing a tooth. And neither one is close to being a reality.

But, the technology is there to replace damaged teeth, joints, heart valves with fake ones. Why isn't anyone creating a thousand "follicular-form implants" as there are dental "root form implants" to drill into the skull? The oral mucosa is as harsh an environment in terms of being exposed to bacteria as the top of the head is. Both are epithelial layers covering a bony base. Both are well-vascularized.

I would be very interested in knowing why hair implants are not being used today. I know people got scared off by the "hair hooks" back in the day, but this is not what I'm talking about. Those were akin to a splinter in your finger, a non-biocompatable material inserted into the epithelial layer. I'm talking about hydroxyapetite coated titanium drilled into pilot holes in the bone, each with a replaceable clip-on hair-like strand of hair like material. This is my vision of the solution to hair loss today.

I have a feeling the problem may be a fear of loss of vascularization with so many implants so close together over the entire scalp, which may impact delivery of blood/oxygen to the vital structures housed within. But I'd imagine there'd be a way around that with creation of groups of hair clusters, which could spread the hair out after a certain length and be unnoticeable