12 replies to this topic

[alc]

Anybody have seen this from LEF:

 

Saving Humans from Premature Death

 

http://health.lifeex...Pages/Stem.aspx

 

Is Longecity community interested in supporting this project?

[sthira]

I saw that, too. And, to build upon your last comments in another thread about SENS, I really think this is the type of stuff SENS should be pursuing. Instead of SENS just asking for more or less random donations that just appear -- from an outsider individual's perspective -- like throwing money away into some unspecified pot or general fund, or whatever, SENS should define a very specific study, write up a brief proposal like LEF here has done, and then make it easy for donors to want to contribute. There could be any number of short studies SENS could be pursuing... C60 in olive oil for example... Why not? What's so hard? Something about metabolism being too incredibly complex for biologists to ever understand or untease.. Or whatever... And yet I'd much rather help fund SENS than LEF. LEF is profit-motivated, writes a shit ton of misleading hyperbole about useless and expensive products; SENS, meanwhile, is a non-profit, and appears genuinely interested in solving the issues of age-related suffering. I'm sure there's something crucial I don't understand about the SENS biz model.

[YOLF]

Personally, I don't like this one... Monthly donations from young for old? I could see taking samples and determining what it is in the blood that old people need, then synthesizing it or growing it in bacteria and then injecting it on a monthly basis or correcting some IPSCs and getting them to grow indefinitely and do infusions of those... but donor blood isn't going to get us very far. 

 

I worry about the risks to the donors. As I understand it, donating stem cells isn't something you want to do a whole lot at this point and it may lead to accelerated depletion. I hope I'm wrong about that... maybe I have old information... or maybe they'll just take one sample per donor... I just think there are better ways to go about this... I really don't like the vampire image...

Edited by YOLF, 08 July 2015 - 11:08 AM.

[niner]

Have they shown this method to work in any species other than humans?  It is crazily expensive to do research with humans.  This experiment looks potentially risky to both donors and recipients; I think they might have a hard time getting it past an Institutional Review Board, assuming LEF would try to do that.  The monthly dosing schedule is rather infrequent, if this is based on heterochronic parabiosis work.  (The stem cell mobilization treatments make it somewhat different than parabiosis.)

[kmoody]

Engraftment of mobilized donor blood stem cells is very low... a couple percent at best, generally much lower. I'm curious if they think that will be sufficient to do anything useful, if they are relying on serum factors rather than cells to exert the positive effects, or if they are planning to do anything special to try to promote engraftment. At n=50 and only $200k/patient (mostly for material costs) I assume they aren't tracking lifespan and may only look at a handful of biomarkers... I'm curious which ones.

 

Regardless, I have a great deal of respect for a wealthy company that is putting its money where its mouth is.

[alc]

I saw that, too. And, to build upon your last comments in another thread about SENS, I really think this is the type of stuff SENS should be pursuing. Instead of SENS just asking for more or less random donations that just appear -- from an outsider individual's perspective -- like throwing money away into some unspecified pot or general fund, or whatever, SENS should define a very specific study, write up a brief proposal like LEF here has done, and then make it easy for donors to want to contribute. There could be any number of short studies SENS could be pursuing... C60 in olive oil for example... Why not? What's so hard? Something about metabolism being too incredibly complex for biologists to ever understand or untease.. Or whatever... And yet I'd much rather help fund SENS than LEF. LEF is profit-motivated, writes a shit ton of misleading hyperbole about useless and expensive products; SENS, meanwhile, is a non-profit, and appears genuinely interested in solving the issues of age-related suffering. I'm sure there's something crucial I don't understand about the SENS biz model.

 

@ sthira -

 

1. one of my concerns with SENS is their ability to attract funds for concrete research that will lead to results in humans. But whenever somebody criticize them for this issue, they act like kids react nervously. They keep refer to the book, etc. I red the book many years ago, and when I have a chance I look at some things there - but there is nothing special about the book, and mre than that some things are just outdated. Do not get me wrong, the book is ok, but again a book that was written 10 years ago, vs latest studies, let's be realistic.

Of course that funding directly a project at SENS will attract more money, than donate in a "general pot". That will also tell about what interest people. The more you like a project, the more you will donate. On the other hand with their portfolio, they can license out technologies (if these technologies really work as they claim) to other companies. And from there they can have tons of funds - even as royalties.

 

2. I'm not too found of LEF, but at least they are trying these things in humans. The main idea is: can we help something like this? Or can we do something that is similar? I look at Alkahest, and seems like they got some funds from Spanish company Grifols -  I would say that is a sign that things are moving in the right direction.

 

Anyway, I think that in 2015 we really need to see human clinical tests, and slow down the exciting news that are found in mice/crickets/worms, etc.

[alc]

Have they shown this method to work in any species other than humans?  It is crazily expensive to do research with humans.  This experiment looks potentially risky to both donors and recipients; I think they might have a hard time getting it past an Institutional Review Board, assuming LEF would try to do that.  The monthly dosing schedule is rather infrequent, if this is based on heterochronic parabiosis work.  (The stem cell mobilization treatments make it somewhat different than parabiosis.)

 

@ niner -

 

1. I do not have any relationship with LEF, so I cannot comment on how thorough and safe their clinical research is laid out.

 

2. Might be very expensive, but isn't that what we are looking for? Personally, I'm tired of great studies in mice/worms/etc. I would say that if a medical technology is mature enough to be tested in humans - and I'm not advocating any blind approach, I'm advocating a solid research - let's find a way to test that sooner and find out if works or not.

 

Your idea, as this is expensive is flawed - sorry to dismantle your logic, and to be honest I prefer not to reply to some of your comments, as you believe I'm attacking you in purpose, and that is NOT the case - anyway, you might think that it's expensive, but let's walk SENS' approach with RMR - they will put lots of money and time in creating that mouse, and then what? You have to walk again the long path to human trials. So that might look like a cheaper solution, but will end up more expensive and even longer in terms of years. Yes, that RMR is "better" then other mice used in tests, but still you have to account for the gap between them and humans. Also, for sure there will be problems, as regardless, the mice are still mice and trials will not translate 100% into humans ... therefore will be a lots of setbacks and lots of  money spent on figure out what the problem is, then fix it.

Again, if we have the option for a technology - that is mature enough - to be tested in humans, then let's do it. There is no point in going around.

[alc]

Engraftment of mobilized donor blood stem cells is very low... a couple percent at best, generally much lower. I'm curious if they think that will be sufficient to do anything useful, if they are relying on serum factors rather than cells to exert the positive effects, or if they are planning to do anything special to try to promote engraftment. At n=50 and only $200k/patient (mostly for material costs) I assume they aren't tracking lifespan and may only look at a handful of biomarkers... I'm curious which ones.

 

Regardless, I have a great deal of respect for a wealthy company that is putting its money where its mouth is.

 

@ kmoody -

 

I watched your company/work and I like much your pragmatic approach. I like that you guys want to see results of much discussed issues in rejuvenation communities. I want to say, that this is what is missing in this field: a practical approach. Somebody that put to test and clarify these issues. "wear and tear" vs "programmed" ... ok, how about designing a study that can clear things out, or point that in fact both affect aging, but in a dual mode?

 

While I do not have any info on LEF's study, I'm very interested in pragmatic approaches to these things. And yes, like I commented above, I would like to see things done in humans if possible.

I believe that in this community there are many people like me that would rather donate to studies like this done by a serious company, that will put to real life test these approaches.

 

Even though a study like Alkahest's will not bring the so dreamed total-rejuvenation, but might be the case that will show a good rejuvenation percentage for brain and couple other organs, I would say that still it's GREAT!

 

I'm not a person that like "empirical" approaches (like heterochronic parabiosis), but still there is nothing wrong with this, as long as is coupled with solid research. We just have to look at Mendeleev empirical approach to compile the periodic table of elements. And yes, if data can be pulled and analyzed from such a study (like Alkahest) , and step by step factors that are "reversing" aging will be discovered, this will be a great approach.

 

Now the question to you: can you guys take a proactive approach and write like a RFP for a similar study to LEF's (or telomerase activation, NAD, or the new study with production of glycine, etc.) and see how much will take to fund one in humans? I bet that the community here will respond favorably and you can get the study under Ichor Therapeutics' umbrella.

 

You can imagine where your company prestige and position will go from there if the study(es) will find out positive outcomes.

[kmoody]

Now the question to you: can you guys take a proactive approach and write like a RFP for a similar study to LEF's (or telomerase activation, NAD, or the new study with production of glycine, etc.) and see how much will take to fund one in humans? I bet that the community here will respond favorably and you can get the study under Ichor Therapeutics' umbrella.

 

At the moment, Ichor's activities are strictly limited to pre-clinical R&D. We are not cGMP or GLP compliant at our facility, and currently lack the regulatory expertise to handle clinical trials in humans. However, we are working to further expand our capabilities and hope to be able to do this sort of work in-house in the near future. The trade off is overhead. Right now we are able to do many studies for far less money than academic institutions or other companies because we have been effective at keeping overhead low. However, the paperwork burden for doing cGMP or GLP work (or human clinical trials) is extensive... prohibitively so, at least for now. As we start to move our product lines towards the clinic, we will obtain the necessary scale and expertise to conduct this sort of work.

 

 

You can imagine where your company prestige and position will go from there if the study(es) will find out positive outcomes.

 

We care a lot more about developing effective therapeutic interventions than bolstering prestige and position. There is plenty of hype in the therapeutics space already, we have no need to contribute to the fluff.

 

You do identify the appropriate focus -- positive outcomes. The reality is that failure rates are high and the ideal pathway to test a therapeutic candidate is not always the best. Even if we had something that was almost certain to work, there are so many non-obvious considerations in the pathway to and through the clinic... there are reasons why promising technologies wash out regularly even though they are shown to work. Understanding those nuances is part of the skill set we are currently obtaining. Why aren't pharma companies grabbing SENS technologies left and right or developing them in house? I think it is because SRF is not adequately addressing these non-obvious nuances and packaging the ideas and tech in a way that makes them appealing. And that is not for lack of effort or incompetence... it is just a very challenging set of skills to learn because it integrates so many complicated disciplines (basic science, medicine, law, regulatory, and business).

 

So in our case, yes, we are aiming to be able to run human clinical trials for all manner of things under the "Ichor umbrella". However, we need to roll out our clinical programs in a pragmatic way, such that we can effectively leverage big money for clinical trials while ensuring that the company remains sustainable. Consider that we could just hit up everyone we know, and maybe piece enough funding together to run a small human trial. However, a better approach might be to further expand our internal capabilities so we are able to do cGMP and GLP, and start handling larger contracts for other pharmaceutical companies. With the overhead covered by contract work, we would 1) be able to build the requisite expertise in-house to pursue our own projects, 2) be able to do this sort of work for the life extension community for less money because our overhead is covered, and 3) be a sustainable company so we could do project after project, rather than being dead after the first one if it doesn't happen to work.

 

I hope this wasn't too long winded, but I wanted to communicate that there are lots of moving parts and it isn't as easy as just putting out a proposal. However, we are headed down the path towards the clinic and will be there soon.

[Danail Bulgaria]

They have written "stem cell-mobilized young human donors". What does that mean? Can some one mobilize his stem cells?

[niner]

 

Have they shown this method to work in any species other than humans?  It is crazily expensive to do research with humans.  This experiment looks potentially risky to both donors and recipients; I think they might have a hard time getting it past an Institutional Review Board, assuming LEF would try to do that.  The monthly dosing schedule is rather infrequent, if this is based on heterochronic parabiosis work.  (The stem cell mobilization treatments make it somewhat different than parabiosis.)

 

2. Might be very expensive, but isn't that what we are looking for? Personally, I'm tired of great studies in mice/worms/etc. I would say that if a medical technology is mature enough to be tested in humans - and I'm not advocating any blind approach, I'm advocating a solid research - let's find a way to test that sooner and find out if works or not.

 

Your idea, as this is expensive is flawed - sorry to dismantle your logic, and to be honest I prefer not to reply to some of your comments, as you believe I'm attacking you in purpose, and that is NOT the case - anyway, you might think that it's expensive, but let's walk SENS' approach with RMR - they will put lots of money and time in creating that mouse, and then what? You have to walk again the long path to human trials. So that might look like a cheaper solution, but will end up more expensive and even longer in terms of years. Yes, that RMR is "better" then other mice used in tests, but still you have to account for the gap between them and humans. Also, for sure there will be problems, as regardless, the mice are still mice and trials will not translate 100% into humans ... therefore will be a lots of setbacks and lots of  money spent on figure out what the problem is, then fix it.

Again, if we have the option for a technology - that is mature enough - to be tested in humans, then let's do it. There is no point in going around.

 

Alc, this isn't the first time you've claimed to "dismantle" my logic without actually having done so.  Don't worry though, as I don't think you are attacking me.  I just think that you evidence the naivete of someone who has never worked in the biomedical field as some of us have.  There are very good reasons to go into animals before you go into humans.  First among them is that killing or injuring humans is considered distinctly bad form.  The second is that a single lab without unlimited resources can do far more experiments in animals than in humans.  When you are trying to do something that has never been done before, a lot of experimentation is needed.  Another reason is that you can control all aspects of the animal experiment, from genetic background to diet to light/dark cycles, while it is very hard to control anything with humans.

 

I'm all for trying to test in humans as soon as a medical technology is mature enough, but they almost never get mature enough without some animal experiments.

[alc]

"Alc, this isn't the first time you've claimed to "dismantle" my logic without actually having done so. "

 

I have not much time to post a lot, like you do, so I'll be just brief . Perhaps you do not understand well what is said by others in some posts and you keep arguing, deviating the discussion to unproductive paths. I looked briefly at some of your posts and high-level logic seems to be an issue for you. No offense but logic and knowledge are somehow disconnected.  You might have the bricks available, but that is not a guarantee that you can build anything but a wall.

You post a lot and you are ubiquitous on this forum, probably that take the toll on the posts you make.

 

  "I just think that you evidence the naivete of someone who has never worked in the biomedical field as some of us have.  There are very good reasons to go into animals before you go into humans."

 

I never said that - but you imply that - again, please read and understand what others say, do not rush to conclusions. My "naivete" approach is based on a nolens volens "exposure" to human clinical research second hand, as my close family worked many years in clinical pharmacology research for one on largest midwest universities, so let's just say I know a lot about those phase I & II "crazy expensive" studies.

I know how studies are initiated in animals then progress in humans. Besides that a large group of our friends work in research and they are either md, md+phd , etc.  I'm not able to pull a diploma in this field like you (as my degrees are in different fields )but  for sure I'm exposed to tons of discussions from real world in this ares. On top of that, I was part of  teams that designed large biotech research facilities, and let's just say I know that aspect well. My comment on your post was, that you want to re-route again this research back into mice, while these guys are ready to move into humans. Move into humans, imply that they already did in animals, so why pull back and bring the study years back? 

 

Also, if you are familiar with projections and life-cycle analysis of complex systems, you will understand well my arguments.

 

 " First among them is that killing or injuring humans is considered distinctly bad form. " ??? - where did you get to this? I don't even like to experiment on mice or other animals, but as of now there are just few in this field thinking . That is why I'm interested in DARPA's approach. FYI: I do not eat meat, except fish, as I like NOT to encourage killing animals (any type/any size).

 

 

"I'm all for trying to test in humans as soon as a medical technology is mature enough, but they almost never get mature enough without some animal experiments." - very good! however like Lao Tzu said, a journey of a thousand miles start with a step. I guess they tested in mice (as is assumed) and ready for humans. So that imply "mature enough". Btw, the project manager of this study is  one of the SENS people, involved with OncoSENS - so this should give you more assurance, I guess?

 

Nota Bene: I want to help rejuvenation/reverse aging process in a meaningful way, not to enter endless argumentation. I rather appreciate an attitude to help this field in a pragmatical way and not arguing things that do not need argued. Good luck with your posts!

 

 

[alc]

Like some of you interested in this study and probably you signed up for updates, I received an e-mail, and seems like they are moving forward.  Let's hope people can donate small sums - I'll try as well - and this study will move forward and provide some good results, that we are all looking for. Again, I have no relationship with them whatsoever, but I like to see pragmatical approaches in this field. Approaches that will show if somethings are working (or point out what is not working).