204 replies to this topic

[resveratrol_guy]

 

Maybe even in less than the proverbial 2 - 5 years?

 

I think the proverbial timespan is closer to 10 years.  Maybe they could do it in less if the treatment includes a plane ticket to another country, for those of us in the US.  But they are a long way from showing that the treatment is safe in humans and that it does something useful.  This is kind of a Phase Zero trial.  The early-adopter customers probably wouldn't care if it was FDA approved or not, but they will want to have some evidence that it works at least reasonably well and isn't going to kill them.  It's going to take a lot of work and money to get from here to there.  Specifically, I think they will ultimately need to take it through the equivalent of FDA's phase 2, as well as probably doing a lot of work on optimizing the protocol.  To do all of this they will need some luck and a lot of money.

 

 

Even 10 years is optimistic, intra-nanny-state. But I think if one were to show up with a suitcase full of money and a plane ticket to the Bahamas, it could happen as soon as 2016. We even have some upper bounds on cost: Liz said they need $250K for 3 Alzheimer's patients, much of which is no doubt allocated to paperwork and analysis, having nothing to do with the procedure itself. And that includes neurosurgery for the intracranial injections. So with high certainty, "plain vanilla" Liz Parrish style therapy costs less than $80K. So yeah, pass me that signup form...

Edited by resveratrol_guy, 13 October 2015 - 03:57 AM.

[sthira]

I think it's really important to NOT take money from the desperately sick and dying to try these (outside of the US) experimental techniques. We need to help fund them, not the family's of the desperate. Even if currently expensive and experimental attempts to cure, say, one person of Alzheimer's find success, that process needs to be accomplished with public, donated funds. Like the American Public Broadcasting donation model: "Viewers Like You."

[Florian Xavier]

she is very optimistic to say the least

Edited by Florian Xavier, 13 October 2015 - 11:55 AM.

[niner]

But I think if one were to show up with a suitcase full of money and a plane ticket to the Bahamas, it could happen as soon as 2016.

 

Well, you could get what Liz got, including all the unknowns.  If you want something that you know has a good chance of working and not harming you, that will take longer, although in the end, it would probably take a much smaller suitcase full of money. 

[Mind]

I think it's really important to NOT take money from the desperately sick and dying to try these (outside of the US) experimental techniques. We need to help fund them, not the family's of the desperate. Even if currently expensive and experimental attempts to cure, say, one person of Alzheimer's find success, that process needs to be accomplished with public, donated funds. Like the American Public Broadcasting donation model: "Viewers Like You."

 

I have to disagree. Personally, I would take the risk if I was in a terminal disease state. I would be furious if someone prevented me from trying an experimental treatment because they thought it was a non-egalitarian process. I would equate such an effort with murder.

[niner]

 

I think it's really important to NOT take money from the desperately sick and dying to try these (outside of the US) experimental techniques. We need to help fund them, not the family's of the desperate. Even if currently expensive and experimental attempts to cure, say, one person of Alzheimer's find success, that process needs to be accomplished with public, donated funds. Like the American Public Broadcasting donation model: "Viewers Like You."

 

I have to disagree. Personally, I would take the risk if I was in a terminal disease state. I would be furious if someone prevented me from trying an experimental treatment because they thought it was a non-egalitarian process. I would equate such an effort with murder.

 

There are two things going on here.  One is the question of access by the terminally ill, and the other is the question of who pays for it.   I'm in favor of allowing the terminally ill to try experimental procedures, as long as there is a reasonable chance that it will do more good than harm.  The question of who pays for it is a much more difficult issue.  Asking the families of the desperate to fund a trial that the usual investment community considers to be a poor risk is problematic.  I don't object to patients paying for the incremental cost of providing the treatment, but if they are also being asked to fund the running of a trial or R&D costs, then they should get a share of the eventual profits from the sale of the treatment, perhaps in the form of stock in the company, or preferably some mechanism that would be less subject to dilution and other shenanigans.

[sthira]

Nothing is ever easy about human animals :-(

But one of the comments Liz Parrish makes that really impresses is they'd like to eventually provide these injections for FREE to everyone. Assuming they work, that is. Meanwhile, we'll stay in the slowly clearing mists of longevity ignorance. All will cost millions, hundreds of thousands, hundreds, then she's hoping governments get behind these efforts -- because it'll bring down medical costs of aging boomers. I wish her well. She seems like a really decent human being, and declares that after conquering human disease, she's moving onto the environment. Shouldn't we all be inspired? I mean, damn...

[ceridwen]

Not many terminally ill people have that much money. I certainly don't

[Decimus]

Good study done on mice using a very similar technique:

http://www.ncbi.nlm....les/PMC3494070/

It gave the mice a nice bounce in MEDIAN lifespan.

[niner]

It's been written up and is being discussed at Technology Review.  FA! also has an ongoing discussion.  It's all worth a look. One of the comments in the TR article, if it's still there, is spam from a company that is doing infusions of "youth factors" that make eveything act youger, or so they claim.  Probably expensive, since they'll pay a 2500 dollar finding fee if you bring them a live customer.  It's not clear what the treatment would be, but it would be done in Kiev or Peru.  (Peru should be nice this time of year...)

[resveratrol_guy]

Good study done on mice using a very similar technique:

http://www.ncbi.nlm....les/PMC3494070/

It gave the mice a nice bounce in MEDIAN lifespan.

 

This is a brilliant contribution. I can't believe I missed this one, as it's been out since 2012.

 

In particular, direct your attention to Figure 3C, where you can see the causes of death in the TERTized mice.  Notice that about 60% of them died with (of?) cancer, which sounds higher than in normal human populations. Moreover, over half of these cancers were lymphomas. But as you can see here and here, the majority of human lymphoma victims are still alive 10 years after diagnosis. Personally, I would rather be fighting one of these less virulent cancers, than random cardiac arrest, or dementia, as a cause of death. So if this data implies that TERT therapy skews the odds in this direction, I think it's a good thing.

[resveratrol_guy]

It's been written up and is being discussed at Technology Review.  FA! also has an ongoing discussion.  It's all worth a look. One of the comments in the TR article, if it's still there, is spam from a company that is doing infusions of "youth factors" that make eveything act youger, or so they claim.  Probably expensive, since they'll pay a 2500 dollar finding fee if you bring them a live customer.  It's not clear what the treatment would be, but it would be done in Kiev or Peru.  (Peru should be nice this time of year...)

 

Nice catch! The spamming company is XVitality. The therapy is implied in the articles to which their webpage links, namely, some form of parabiosis. (Note that none of those articles mentions them, so they're trying to ride a hype wave here.) Either they're getting blood from some dodgy source, or they're injecting folks with GDF11 to mimic the benefits, or they're just lying about it. Just to be pompous about it, I predicted this on 1/22/2015. So let me guess... next month we're going to have TERT clinics in Bananastan?

[alc]

new interview with Liz Parish:

 

 

[corb]

a

 

Good study done on mice using a very similar technique:

http://www.ncbi.nlm....les/PMC3494070/

It gave the mice a nice bounce in MEDIAN lifespan.

 

This is a brilliant contribution. I can't believe I missed this one, as it's been out since 2012.

 

In particular, direct your attention to Figure 3C, where you can see the causes of death in the TERTized mice.  Notice that about 60% of them died with (of?) cancer, which sounds higher than in normal human populations. Moreover, over half of these cancers were lymphomas. But as you can see here and here, the majority of human lymphoma victims are still alive 10 years after diagnosis. Personally, I would rather be fighting one of these less virulent cancers, than random cardiac arrest, or dementia, as a cause of death. So if this data implies that TERT therapy skews the odds in this direction, I think it's a good thing.

 

I think I've read that mice have a higher cancer incidence than humans generally so there might not be that much of an increase. Even in relation to this (or a similar) particular paper I think that was used as an argument that it might be safe for humans. I have the vague memory of reading an article with this line of thought anyway.

 

Considering these mice lived longer than normal (albeit median lifespan) the increase of cancer is also not a surprise if there is any.

That being said their slight increase of lifespan in general was proof to most people back in 2012 that telomerase really isn't a major player in aging because in a mouse 15~25% even though it sounds like a big increase is actually quite negligible it's about a 100 days or so and it can easily be replicated with CR and you'd have to wonder how much of the increase was actually due to CR. Most labs fail to measure callorie intake properly when running other experiments. Lots of lifespan studies have been adjusted for CR lifespan increase since then because they failed to replicate increase in an overfed animal, there was even an article posted on the news forum about it months ago.

 

Anyway the argument that maybe the therapy wasn't perfect in delivering the payload is valid as well, so you know, as anything in biology that hasn't been tested into the dirt we have to remain on the fence, and I'm trying my hardest to do so.

On the off chance of proving to be usable as a treatment for disease like AD I've remained interested since those papers were published, but not optimistic. Even if mechanistically long telomerase improves general health in humans I'm not sure we'll have a proper vector of delivery in the short (20 yearsish) term. There's no massive drive to develop non viral delivery vectors yet. Except for HIV. Of course my guess is if TERT is that beneficial that might change.

 

 

[resveratrol_guy]

That being said their slight increase of lifespan in general was proof to most people back in 2012 that telomerase really isn't a major player in aging because in a mouse 15~25% even though it sounds like a big increase is actually quite negligible it's about a 100 days or so and it can easily be replicated with CR and you'd have to wonder how much of the increase was actually due to CR. Most labs fail to measure callorie intake properly when running other experiments. Lots of lifespan studies have been adjusted for CR lifespan increase since then because they failed to replicate increase in an overfed animal, there was even an article posted on the news forum about it months ago.

 

How could the benefit have been due to CR? There was a control group in this study. It would have taken deliberate effort to feed the TERT group less.

 

Nonetheless, I take your implied point which is that 20% life extension in mice is unremarkable. But even if the affected pathways completely overlap with CR, it would be nice to lead a CR quality of life, without the actual restriction.

 

As to AD, I think the basis of their proposal actually has more scientific merit than the sort of generalized therapy which Parrish received, in particular, the TERT-excludes-phosphotau paper which Steve H presented above. Rarely in biology do you find such clean exclusions. That said, I think the idea of targetting the hippocampus in isolation is not going to cut it in late stage patients in their proposed trial. What's sad is that such a therapy might actually cure the disease in mild cases, but if the funding decisions are made based on the first trial results, they're never get there.

[Rocket]

Has Bioviva said anything about the specifics of the TERT and myostatin treatments?  Apparently the myostatin gene therapy was first tested on a male doctor 5 years ago, so Liz Parrish is not patient zero with that, only the TERT activator.  There should be some literature out there about what specifically they are using.  Are the gene therapies available through biomed companies that sell premade viral vectors?

[alc]

@ Rocket -

 

"Are the gene therapies available through biomed companies that sell premade viral vectors?"

 

Milo Biotech is using AAV

 

"
Current Pipeline

Our objective is to develop a gene therapy as a one-time treatment option for muscle wasting diseases.

We currently have three active clinical programs for Becker Muscular Dystrophy, Inclusive Body Myositis and Duchenne Muscular Dystrophy.

We are also testing different administration routes with different viral serotypes."

 

http://milobiotechnology.com/pipeline/

 

 

"

Our approach represents a highly potent therapy for patients with severe muscle wasting.

Our pre- and clinical stage programs reflect the versatility of our technology. Although not curative, Follistatin gene therapy has the potential to significantly

improve quality of life by increasing muscle function and modulating pathological fibrosis."

 

 

Here are the clinical studies:

 

http://milobiotechno...com/technology/

 

http://www.ncbi.nlm....pubmed/25322757

 

 

 

 

[Lebombo]

This is amazing work.  Look forward to the outcome.  Hope it turns out good and we learn a lot in the process.

[Logic]

Is it just me or has Liz been very quiet since the interviews etc just after therapy?
Is there any news on how she is doing currently? I don't see any?

[Steve H]

Their face book page and twitter are active and she has been doing interviews. However I guess it is a case of nothing to report until the data is in.

[corb]

Their face book page and twitter are active and she has been doing interviews. However I guess it is a case of nothing to report until the data is in.

 

No news is good news.
As long as she's healthy people's trust in gene therapy will grow.

If something good comes out of that particular therapy that's an added benefit but the big thing is proving to the mainstream gene therapies are not scary.

[Iporuru]

From David Kekich's "Longevity News Alert":

 

December 15, 2015

 

Anti-Aging Conference Report

 

Dear Future Centenarian,  

 

The Holiday Season is time to be merry… not morbid. Lots of parties, family get togethers, exchanging gifts, Christmas Carols and good cheer for all… except for the billions who celebrated their last Christmas over the centuries.

 

Joyfully, people all over earth come together during this very special time of year. Merriment, good times and tons of love spread around the world. Sadly, it will be the last one for millions.

 

Kat Cotter and I spent last weekend in Las Vegas where we got together with Liz Parrish, Greta Blackburn, Bill Andrews, Terry Grossman, Jason Williams and some other special people in my life at the annual American Academy of Anti-Aging Medicine show.

 

Vegas is Vegas. Most gather there for mindless fun and gambling. We had fun too, but were there for an entirely different reason than most. It was part of our committed pursuit of healthy longevity… to help ensure fewer Holiday seasons are missed in the coming decades.

 

Liz was in top form, showing off her new musculature and diminishing wrinkles from her recent gene therapy. Although she may have taken what was a limited dose, she is already showing small but definite improvements… about six weeks ahead of schedule. It was funny how people were jockeying for position to be next in line for treatments.

 

Edited by Iporuru, 23 December 2015 - 04:41 PM.

[Steve H]

Show me the data! I have seen the baseline data but nothing since.

[Iporuru]

They will show the data; we just have to wait.

 

Another fragment from December 9, 2015 issue of the "Longevity News Alert":

 

(...) One of our costumed guests, Liz Parrish (not shown), demonstrated some early subtle progress from her September gene therapy. We thought it would take 4-5 months before we could measure anything positive, but indications already show we could have early supporting evidence of a regenerative therapy in the relatively near future. (...)

[Mind]

I think what Liz is doing is great. Praise for the risk-takers.

 

However, saying "she is showing progress" without any hard data, or even comparison pictures, is a disservice to the life extension community.

 

Don't forget how powerful the placebo effect can be.

[Steve H]

It screams hype to me. Data or it did not happen. I admit she looks fantastic and even better lately but the researcher in me wants to see those metrics. 

 

Edited by Steve H, 23 December 2015 - 08:00 PM.

[niner]

I agree with you guys that this isn't a very useful report.  Liz is a beautiful healthy young woman.  She's not sarcopenic and she is unlikely to suffer from short telomeres, so what exactly should we expect to see anyway?  Myostatin inhibition doesn't do much on its own-- you have to work out.  I've just come off of two months of experimentation with an oral myostatin inhibitor, and I'll tell you what it did for sure:  It made me work out harder and pay more attention to getting the protein I needed to build muscle.  So guess what?  I got stronger and feel great.  I'm thrilled with the outcome, but I have no idea if the myostatin inhibitor is responsible, or if it was the other stuff.  This is the exact kind of thing where you can't learn anything without a placebo control.  With the HTERT part of Liz's experiment, we can at least see the effect on fraction of short telomeres, if it wasn't negligible to begin with.  Something might show up in other biomarkers, but it will be confounded by any changes in her activity, diet, stress level, etc.  I hope that something really impressive happens, so that there isn't any question about what caused it.  I want her experiment to "work", and to expand possibilities for treatment of others.  That would be a fantastic outcome, but the realist in me assigns this a low probability.

[marcobjj]

 

 

Considering these mice lived longer than normal (albeit median lifespan) the increase of cancer is also not a surprise if there is any.

That being said their slight increase of lifespan in general was proof to most people back in 2012 that telomerase really isn't a major player in aging because in a mouse 15~25% even though it sounds like a big increase is actually quite negligible it's about a 100 days or so and it can easily be replicated with CR

 

 

 

A single inoculation of a TERT carrying virus extending their lifespans in 14% to 23% is impressive, as AAV viral activity (supposedly) doesn't persist over the long term. The paper mentions viral transduction efficiency of 20–50%  after one month. Multiple inoculations could yield   a much greater lifespan extension.

 

 

 

 

 

and you'd have to wonder how much of the increase was actually due to CR. Most labs fail to measure callorie intake properly when running other experiments. Lots of lifespan studies have been adjusted for CR lifespan increase since then because they failed to replicate increase in an overfed animal, there was even an article posted on the news forum about it months ago.

 

The TERT trated mice made lifespan gains against the control group. So unless AAV9-mTERT works as an appetite suppressant somehow, I think the study was controlled for CR.

 

 

 

 

 

Good study done on mice using a very similar technique:

http://www.ncbi.nlm....les/PMC3494070/

It gave the mice a nice bounce in MEDIAN lifespan.

 

This is a brilliant contribution. I can't believe I missed this one, as it's been out since 2012.

 

In particular, direct your attention to Figure 3C, where you can see the causes of death in the TERTized mice.  Notice that about 60% of them died with (of?) cancer, which sounds higher than in normal human populations. Moreover, over half of these cancers were lymphomas. But as you can see here and here, the majority of human lymphoma victims are still alive 10 years after diagnosis. Personally, I would rather be fighting one of these less virulent cancers, than random cardiac arrest, or dementia, as a cause of death. So if this data implies that TERT therapy skews the odds in this direction, I think it's a good thing.

 

 

Right in the abstract, it is mentioned that: "Importantly, telomerase-treated mice did not develop more cancer than their control littermates, suggesting that the known tumorigenic activity of telomerase is severely decreased when expressed in adult or old organisms using AAV vectors. "

Edited by marcobjj, 20 January 2016 - 11:16 AM.

[Steve H]

I think the jury is still out on telomerase. In my view transient telomerase activation could be useful in therapies that require rapid wound healing for example and perhaps organ repair as the Blasco lab demonstrated in heart attack induced mice:

 

http://www.ncbi.nlm....pubmed/25519492

 

Will it become a mainline age reversal therapy? I suspect not until further confirmation either way of the risks are made. It is permissive of cancer but on the other hand longer telomeres means a more stable genome so offers a level of cancer protection. It will of course remain in use for stem cell work where expansion of cell populations is needed etc...  

 

However it is not a magic bullet and will not control aging fully as glucosepane, Lipofuscin, amyloids and other accumulated cellular waste will still continue to build up and destroy the systemic signalling environment leading to decline of stem cell function and repair. I think people like Bill Andrews are wildly optimistic about its potential and science has moved on considerably since the 90s when telomerase was discovered. Blasco and Fossel give far more grounded reasoning for why telomerase could be useful. 

Therefore addressing the root of the telomere attrition would make the most sense ala SENS rather than attempting to "patch up" the problem downstream which effectively this is doing. 

I personally find the Follistatin therapy more potentially interesting as FSTN can reduce TGF-beta levels which are a big driver of systemic signalling decline.

However so far all I hear from BV is chatter about how we should do something about aging (well duh!) and not a single piece of data aside from the Milo Biotech data for FSTN efficacy of course. I shall remain neutral until we see the data, assuming this ever surfaces.

[Florian Xavier]

" as FSTN can reduce TGF-beta levels which are a big driver of systemic signalling decline."

 

 

any proof ?