217 replies to this topic

[Bryan_S]

 

You can buy it for yourself today, but at expensive micro lab quantities on Amazon. Alkahest and Tony Wyss-Coray are making a run at it as well. In the next 5 years who knows. But the research has to be funded and capital invested. And NIH-funded research is at historically low levels so investors are needed. Lets see how it plays out and hope for the best.

 

I know this is hard to believe, but the vitamin and supplement market is so massive that even some of the *retailers* in this business run public companies with market capitalizations over $1 BILLION USD.  See for example Vitamin Shoppe, NYSE symbol VSI.   There are many many manufacturers of supplements with valuations over $1 billion.

 

IF there is demand...and IF there is no regulation on supply...for one of these companies to invest $5M in startup costs to support a unique production process for GDF-11 would be *spit money*.   Even if you make pessimistic estimates, assume 2% of 80M aging US citizens are willing to pay $300/year for GDF-11 supplementation, that is a $480 MILLION USD market.  And that is the US alone.   It's very easy to build a return on investment case to invest $5M when you are comparing it against an unregulated large market of that size.

 

Contrast that to a highly regulated pharmaceutical.   Because of the FDA meddling, the $200M startup cost requires you to find a multi-billion dollar payoff to justify the huge risks and large number of likely failures.   It's a totally different case.

 

 

If you want to make it, I'm 100% behind you but don't delude yourself. If I like what I see I'll help promote it, but I believe we still need more data. GDF11 isn't as effective as whole blood or plasma because other factors are working together. Once the proper cocktail is determined as I eluded to before several factors will be combined so as to give similar results to the parabiosis experiments. GDF11's scope is still impressive, but alone I don't see the hype as reality.

[free10]

 

 

Doesn't cancer travel via the blood? Would there be a risk of 'catching' someone else's cancer that way? 

 

This looks to be able to filter cancer and many other substance out of the blood and trap them in the filters.

 

The donor gets his cells back and everything is separated via Plasmapheresis. No cells are transferred in the plasma treatments. The researchers just want the proteins. Is this what you were asking?

 

I'm on the road right now so I apologize if I'm not seeing the question right.

 

 

What you want in what the filter and is designed to do, is pull the cells out you want out of the blood while letting the blood with them flow back into the donor. What I am saying is if the filter is designed for say GDF-11, then it can be isolated in the filters, while allowing the rest of the blood back into the donor, and then you could then empty the filter out of the GDF-11 or whatever youth factors, and put just that into a recipient. In fact it could even be used with animals, to filter it out of their blood for human use for a rather natural and endless supply. Now I am not an expert on any of this but it would seem to make sense, and I do know young human blood was given to an old mouse, and it had the same effect on them as young mouse blood did.

 

Now, with that said I think there is something else is going on at the same time in these experiments they may not have guessed yet, if they are doing them as I suspect they would. I would guess they are pulling the old blood out to replace it with some of the young, and that may have benefit right there. Since old blood seem poisonous to the young, though I could have that wrong. But if I have that right, we then could filter them out of our own blood that would be harming us.

 

Just my thoughts.

[Bryan_S]

The link I posted didn't say for sure how they were doing it. "The PLasma for Alzheimer SymptoM Amelioration (PLASMA) Study"

[niner]

The Clinical Study that you linked says the patients are getting one unit of plasma a week for four weeks.  That really isn't very much.  It seems to me that in order to compare it with parabiosis, they should get more like a unit a day, or maybe more.  What if GDF11 has a short half life?   Also, parabiosis is blood exchange, not plasma.  What if the cells are part of the magic?  The problem with a poorly designed study is that when it fails, no one wants to repeat it, because everyone "knows" that it doesn't work.  I hope they get enough of a signal out of it to get people to express a bunch of GDF11 and move forward with it.

[ceridwen]

How can one get onto the clinical trial. There doesn't seem to be a contact number or anything

[pone11]

How can one get onto the clinical trial. There doesn't seem to be a contact number or anything

 

There are only 18 alzheimer's patients in the study.   I'm sure it is filled.   Look for a new study.

[ceridwen]

Ok thanks
Ok thanksbut it looks as if it is still open

[pone11]

Ok thanks
Ok thanksbut it looks as if it is still open

 

They began the treatments in October.

[free10]

I think they are doing two trials with on in California and another one in Australia. When the mice were given blood injections it was 3 a week. When they used just the GDF11 they said they never got it over 60%, of young levels in them. No idea of how many times a week they gave that to them.

[free10]

On the once per week, my best wild guess is they are starting out cautious on this and may adjust frequency and amounts with time.

 

[ceridwen]

Does anyone know where the Australian trials are and how to get on to them?.

[pone11]

I think they are doing two trials with on in California and another one in Australia. When the mice were given blood injections it was 3 a week. When they used just the GDF11 they said they never got it over 60%, of young levels in them. No idea of how many times a week they gave that to them.

 

In Harvard study mice were injected with GDF11 daily, I believe.

[pone11]

On the once per week, my best wild guess is they are starting out cautious on this and may adjust frequency and amounts with time.

 

Of course, but like others I don't understand why they wanted to start with alzheimer's.   If they had started with early stage dementia they would have a better shot at low doses showing remarkable and measurable reversals.  That would have brought in a lot of research money to continue other types of testing.   By shooting for the moon and going for alzheimer's, they risk showing only insignificant reversals and stalling the project.

[free10]

 

On the once per week, my best wild guess is they are starting out cautious on this and may adjust frequency and amounts with time.

 

Of course, but like others I don't understand why they wanted to start with alzheimer's.   If they had started with early stage dementia they would have a better shot at low doses showing remarkable and measurable reversals.  That would have brought in a lot of research money to continue other types of testing.   By shooting for the moon and going for alzheimer's, they risk showing only insignificant reversals and stalling the project.

 

 

Maybe that's who volunteered first. Maybe. They are starting with stage 1 and stage 2 alzheimer's, as I understand or remember it. I would have wanted probably to start with heart failure, since they could see and measure the results with machine data, which would or should be harder to argue with if it showed signs of working.
 

[Bryan_S]

Does anyone know where the Australian trials are and how to get on to them?.

 

ceridwen, you'll just have to keep your eyes open. This is the next one I see and there could be others in the works.

 

If this article is correct they may hold it at the Joslin Diabetes Center if it all comes together.

http://hsci.harvard....ce-made-younger

[niner]

If this article is correct they may hold it at the Joslin Diabetes Center if it all comes together.

http://hsci.harvard....ce-made-younger

 

Thanks for that link, Bryan.  As for a timeframe for human studies, they said this:

 

 

Rubin, and Wagers, who also has a laboratory at the Joslin Diabetes Center, each said that, baring unexpected developments, they expect to have GDF11 in initial human clinical trials within three to five years.

 

 

If 3 years is the short end of the range, that's kind of disturbing.  I'd like to think we could trial it ourselves in less time than that.  It's frustrating how slow biomedical research moves. 

[pone11]

 

If this article is correct they may hold it at the Joslin Diabetes Center if it all comes together.

http://hsci.harvard....ce-made-younger

 

Thanks for that link, Bryan.  As for a timeframe for human studies, they said this:

 

 

Rubin, and Wagers, who also has a laboratory at the Joslin Diabetes Center, each said that, baring unexpected developments, they expect to have GDF11 in initial human clinical trials within three to five years.

 

 

If 3 years is the short end of the range, that's kind of disturbing.  I'd like to think we could trial it ourselves in less time than that.  It's frustrating how slow biomedical research moves. 

 

 

What is even more disturbing to me is that the Harvard researchers are in discussions with "venture capitalists" to fund further human research.   That suggests that everyone involved wants to make a buck for themselves, and it's not about pure science.   They will distort things to encourage use of proprietary variations rather than doing what is best for mankind and analyzing the use of a generic low-cost protein GDF11.

[Bryan_S]

niner, I don't know what to say other than there is a ton of Gov. red tape. The Plasma study got started first because transfusing blood components is an already common procedure with plenty of history. 

 

There was a guy who showed up last year who said he was starting a human trial but he didn't produce any contact info or provide enough details.

http://www.longecity...arch-gdf11-etc/

 

We also stalled on the group buy discussion.

http://www.longecity...df11-group-buy/

 

This thread also:

http://www.longecity...ng-legal/page-3

 

 

pone11 "Harvard researchers are in discussions with "venture capitalists""

I also looked at the investment angle and they are a close nit group of investors as you noted and I didn't see an immediate way to get involved. They are positioning this as a big buisness venture from either study.

 

Here was a good article from December.

http://www.bioscienc...4-breakthrough#

 

"Wagers is headed for clinical trial as well, but wants to answer many questions first. Her group has finished the first of three studies gauging how long effects of GDF11 last. The above 2005 papershowed effects of parabiosis lasted three weeks, the time span studied. “A really important question is `Do you need to continuously supply the factor, or does it re-set the system?’ So far there is some evidence it re-sets.” The Stanford transfusion work is encouraging as “it says whatever activity is causing the changes persists in plasma for a period of time.” Aging may be about “imbalance of signals.”"

Edited by Bryan_S, 18 January 2015 - 10:52 PM.

[Bryan_S]

Reversing Aging Processes with One Protein: A 2014 Breakthrough

 

What I find interesting is that we may not have to worry about our accumulated DNA damage. “After treatment with GDF11 we see cells no longer carry DNA damage. So it is unlikely we are causing a proliferation of DNA-damaged cells. But to make sure nothing in the DNA repair process goes awry, we have treated mice for 60 days with GDF11. There is no increased incidence of tumors. But we are gearing up to go longer and use more sensitive models.” That the protein prompts some DNA repair is a huge advantage, as there are worries with other techniques that DNA can be damaged. “And it is really exciting that GDF doesn’t select for certain cells. It looks like this happens to every cell.”

 

What also peeks my interest is the application of GDF-11 may reset levels for the whole system. At this point it "appears" you may not have to continuously take these blood factors in a maintenance regimen. Wagers is headed for clinical trial as well, but wants to answer many questions first. Her group has finished the first of three studies gauging how long effects of GDF11 last. The above 2005 paper showed effects of parabiosis lasted three weeks, the time span studied. “A really important question is `Do you need to continuously supply the factor, or does it re-set the system?’ So far there is some evidence it re-sets.” The Stanford transfusion work is encouraging as “it says whatever activity is causing the changes persists in plasma for a period of time.” Aging may be about “imbalance of signals.”

 

These are 2 important developments and the DNA repair insight intuitively makes sense. Our DNA is under assault from the day we are born, yet in most cases we don't see tumors and cancers manifest until later in life. Maybe GDF-11 is re-initiating a DNA maintenance protocol that with aging somehow slowly gets turned off or damaged cells are outright destroyed.

 

Wagers is looking for the tissues that generate GDF-11. Her group has narrowed the source of GDF11 to three different cell types. They want to either discover a way to naturally stimulate its production or possibly increase the number of cells that produce it.

 

Still all speculation until Wagers completes her next 2 studies. So we can begin to see why she hasn't rushed into human clinical trials, she wants to answer a few questions first. 

[pone11]

Reversing Aging Processes with One Protein: A 2014 Breakthrough

 

What I find interesting is that we may not have to worry about our accumulated DNA damage. “After treatment with GDF11 we see cells no longer carry DNA damage. So it is unlikely we are causing a proliferation of DNA-damaged cells. But to make sure nothing in the DNA repair process goes awry, we have treated mice for 60 days with GDF11. There is no increased incidence of tumors. But we are gearing up to go longer and use more sensitive models.” That the protein prompts some DNA repair is a huge advantage, as there are worries with other techniques that DNA can be damaged. “And it is really exciting that GDF doesn’t select for certain cells. It looks like this happens to every cell.”

 

What also peeks my interest is the application of GDF-11 may reset levels for the whole system. At this point it "appears" you may not have to continuously take these blood factors in a maintenance regimen. Wagers is headed for clinical trial as well, but wants to answer many questions first. Her group has finished the first of three studies gauging how long effects of GDF11 last. The above 2005 paper showed effects of parabiosis lasted three weeks, the time span studied. “A really important question is `Do you need to continuously supply the factor, or does it re-set the system?’ So far there is some evidence it re-sets.” The Stanford transfusion work is encouraging as “it says whatever activity is causing the changes persists in plasma for a period of time.” Aging may be about “imbalance of signals.”

 

These are 2 important developments and the DNA repair insight intuitively makes sense. Our DNA is under assault from the day we are born, yet in most cases we don't see tumors and cancers manifest until later in life. Maybe GDF-11 is re-initiating a DNA maintenance protocol that with aging somehow slowly gets turned off or damaged cells are outright destroyed.

 

Wagers is looking for the tissues that generate GDF-11. Her group has narrowed the source of GDF11 to three different cell types. They want to either discover a way to naturally stimulate its production or possibly increase the number of cells that produce it.

 

Still all speculation until Wagers completes her next 2 studies. So we can begin to see why she hasn't rushed into human clinical trials, she wants to answer a few questions first. 

 

I had taken away most of the same points from reading the same articles earlier.   But don't you think the fact that parabiosis effects start to wear off after three weeks - combined with the fact that GDF-11 by itself shows less impact than parabiosis or transfusion - would suggest that GDF-11 by itself is not doing any permanent reset?   I understand in one of the early 2014 mice studies they were injecting the mice with GDF-11 daily.

 

Many of us wonder why they don't do more human studies, but the thought occurs that at the current prices for GDF-11, daily administration to a large group of humans would be a HUGELY expensive undertaking, and who is going to subsidize that cost when there is no proprietary drug on the back end of research to subsidize the investment?

 

This is the kind of thing that a very rich foundation or individual needs to sponsor.

[Bryan_S]

I had taken away most of the same points from reading the same articles earlier.   But don't you think the fact that parabiosis effects start to wear off after three weeks - combined with the fact that GDF-11 by itself shows less impact than parabiosis or transfusion - would suggest that GDF-11 by itself is not doing any permanent reset?   I understand in one of the early 2014 mice studies they were injecting the mice with GDF-11 daily.

 

Many of us wonder why they don't do more human studies, but the thought occurs that at the current prices for GDF-11, daily administration to a large group of humans would be a HUGELY expensive undertaking, and who is going to subsidize that cost when there is no proprietary drug on the back end of research to subsidize the investment?

 

This is the kind of thing that a very rich foundation or individual needs to sponsor.

 

 

"But don't you think the fact that parabiosis effects start to wear off after three weeks." Three weeks was the length of the study and she didn't mention a post decline. This statement was made about the effects of "parabiosis," she did not mention this in the context of GDF11 given alone but it does make sense that it might work but maybe not as effectively. Her group has finished the first of three studies gauging how long effects of GDF11 last. Parabiosis seems to be superior and a far more encompassing approach because that blood contains everything. I do think the full cocktail of growth factors is preferable to GDF11 alone. To synthesize that will require a lot more research/study to provide answers to the proper ratio of proteins.

 

Think about it, If levels can be kick started again after revitalizing the hosts cells to a younger state, that might mean after your initial treatment, maybe maintenance treatments could be pushed off months or even years. Thats my take away. This research is just scratching the surface.

 

As yet no one has mentioned animal/human chimeras for blood plasma production. It could be a cheep source of GDF11 and the cells could be programed to produce higher amounts of the desired blood factors and the blood cells could be returned to the animal host and the plasma concentrated. Sounds gruesome but why not?

 

For the conventional approach I've looked up Human GDF11 Plasmids and if you want to brew up your own Escherichia coli bacteria all the raw materials are available for those skilled in the art. I haven't worked out the startup costs to make your own strain of E.coli for GDF11 expression yet. In fact you might be able to buy E.coli already engineered for the task, but using a patented strain for commercial production might be a problem if its not your creation. The protein purification might be the hardest task. I'm looking at separation techniques online now. However at $3,900 per mg someone has to figure this out.

Edited by Bryan_S, 22 January 2015 - 07:11 AM.

[ceridwen]

Blood transfusions are not so expensive. Why can't we do it with transfusions? There must be people out there willing to donate.

[Bryan_S]

Blood transfusions are not so expensive. Why can't we do it with transfusions? There must be people out there willing to donate.

 

I talked with a guy I know at One Blood and they are not geared up for something like this. If this practice began it could easily outstrip supply and how much of a premium would you be willing to pay over what they sell it to hospitals for? We would want them to classify blood by donor age and in effect draw down the young supply, which there isn't much.

 

Who donates blood anyway? http://www.bloodcent...blood-banking/ "According to studies, the average donor is a college-educated white male, between the ages of 30 and 50, who is married and has an above-average income. However, a broad cross-section of the population donates every day. Furthermore, these “average” statistics are changing, and women and minority groups are volunteering to donate in increasing numbers. While persons 65 years and older compose 13 percent of the population, they use 25 percent of all blood units transfused." So we'd have to appeal to college students and they would want to be paid unlike blood donors who give it for free.

 

Oh and then The Nation Has a Major Blood Shortage which is the current reality.

 

So if blood costs around $300 a pint what would be fair for someone just wanting to boost their blood factors? Maybe 2 or 3 times the price considering the scarcity of blood from young donors.

http://www.forbes.co...ood-for-profit/

 

It doesn't look easy but it could be done for a price.

Edited by Bryan_S, 22 January 2015 - 09:15 AM.

[ceridwen]

That's no good.I'm in Europe

[niner]

However at $3,900 per mg someone has to figure this out.

 

Unusual chemicals and biologics have crazy prices when demand is low.  The prices have very little to do with the cost of production.  If someone gets a decent expression system going, and grows up a large quantity of cells, then prices will drop dramatically.   If you look at the cost of the various anti-tnf mabs (Enbrel, etc), that might give you a better idea of the cost.  I'd expect that to be more like a ceiling than a floor on the price, too, although that is ultimately determined by supply/demand and insurance reimbursement.
 
Here's a ten-year-old example of an effort to improve the expression rate of TGF beta, a protein very similar to GDF11.  They got an order of magnitude improvement there.  A major question is what dose would be needed, how often, and for how long.
 

Protein Expr Purif. 2004 Oct;37(2):265-72.
Overexpression of human transforming growth factor-beta1 using a recombinant CHO cell expression system.
Zou Z, Sun PD.

Transforming growth factor-beta1 (TGF-beta1) is secreted by most cells as a high molecular weight latent complex, which consists of latent TGF-beta1 disulfide bonded to latent TGF-beta1-binding protein (LTBP). Current recombinant expression systems yield less than 1-2 mg of the mature TGF-beta1 per liter of cell culture medium. In an effort to produce large quantities of the recombinant cytokine for structural studies, we have constructed a mammalian expression system based on a modified pcDNA3.1(+) vector with a glutamine synthetase gene inserted for gene amplification. The leader peptide of TGF-beta1 was replaced with that of rat serum albumin, and an eight-histidine tag was inserted immediately after the leader sequence to facilitate protein purification. In addition, Cys 33 of TGF-beta1, which forms a disulfide bond with LTBP, was replaced by a serine residue. The resulting expression construct produced a stable clone expressing 30 mg of mature TGF-beta1 per liter of spent medium. Purified TGF-beta1 bound with high affinity to its type II receptor with a solution dissociation constant of approximately 70 nM, and was fully active in both a Mv1Lu cell growth inhibition assay and in a PAI-1 luciferase reporter assay. Owing to similarities in the synthesis, secretion, and structure of TGF-beta family members, this recombinant expression system may also be applied to the overexpression of other TGF-beta isomers and even to members of the TGF-beta superfamily to facilitate their preparation.

PMID: 15358346

[Bryan_S]

 

However at $3,900 per mg someone has to figure this out.

 
If you look at the cost of the various anti-tnf mabs (Enbrel, etc), that might give you a better idea of the cost. 
 
Here's a ten-year-old example of an effort to improve the expression rate of TGF beta, a protein very similar to GDF11.

 

 

Thanks,

 

Chinese hamster ovary (CHO) cells, interesting method. Superior process for high quality proteins but it carries a very high price tag over Escherichia coli bacterial systems and generates lower volumes. Its also a recommended BSL-2 environment setup and very slow growing compared to E.coli.

 

I'm no expert but we kicked this around several months ago debating if the protein needed the proper glycosylation, which mammalian expression systems are known for. 

 

I looked up GDF-11 on the OriGene website, I picked them because they market some pretty good mammalian cell expression systems. The GDF-11 product they sell is derived from E.coli. Also every one else is doing it the same way. Now, that's not to say it's the correct way but its likely the cheapest production method for this particular protein, at this time.

 

As to the bioactivity of the GDF-11 in the Amy Wagers study this could be the reason her results were not as spectacular with the GDF-11 alone and this could have been a quality issue related to E.coli production. The article noted; A last consideration, she said, was “practical. The recombinant GDF11 protein is available commercially so we could quickly test impact of changing levels.” Could be there was no commercially available mammalian processing systems to order the protein from. For her study, the E.coli produced GDF-11 was bioactive enough to see the desired lab results. Without questioning the good doctor its hard to say.

 

Someone down the line will have to do a comparison of the effectiveness of GDF-11 produced from the different expression systems to see if a mammalian cell system is warranted?

[Bryan_S]

Ageing research: Blood to blood

21 January 2015 NATURE | NEWS FEATURE

 

Pretty interesting article on how the research brought us to this crossroads with GDF-11.  

[Bryan_S]

That's no good.I'm in Europe

 

ceridwen, once this is proven and the risks are known, it will be available at some price. It is already for lab quantities, if you have deep pockets but even so we still don't know the appropriate dosages. If these proteins are not made cost available to us, it can be imagined, that a younger family member could donate his or her blood factors to their elders. Some may even choose to bank plasma aside for the days to come. See link to research push. Needless to say there is interest reawakening in Freeze-dried Plasma which is a fairly mature technology dating back to the 1940's. Here was a recent study. Its important to note these studies have not assessed the shelf life of the blood factors we are discussing here. This research has been driven for trauma in areas away from hospitals, and mainly to stabilize the injured. Also we still don't yet know how frequently this plasma will need to be given to yield the proper results however this could be one strategy to bank it. In essence this could one day become a family affair where our young help the old.

[Bryan_S]

http://www.amazon.co...-keywords=GDF11

 

Is anyone else seeing this? An explosion of GDF-11 products listed on Amazon.

[Bryan_S]

Has anyone seen the frenzy a GDF11 researcher can generate on an open internet forum? 283 question posts in less than 15-hours. See Dr. Saul A Villeda's research. There are some pretty thought provoking questions he's generated here. It will be interesting to see the answers start to trickle in. There is no way this guy can answer all these questions.  http://www.reddit.co...da_i_research