More Trials and Cost Effective Trials of Rejuvenation Therapies are Much Needed
It costs a great deal to run a reasonably sized clinical trial within the formal system of regulatory governance. If the goal is to make a compelling demonstration of effectiveness, then at the very least a larger-than-usual phase 2 trial is required. The cost of getting to that point is upwards of $15-20 million in industry, and still a substantial fraction of that for academic institutions that have much of the supporting infrastructure already in place. Yet groups like Lifespan.io can put together a less formally administered trial, one that will teach us almost as much about whether or not a given approach is efficacious, for less than $250,000.
Not enough of this sort of work is taking place. There are too few low-cost assessments carried out with the aim of generating good data that may otherwise never arise. Even just looking at senolytics, there are scores of age-related conditions that may be beneficially effected by the low-cost dasatinib and quercetin combination. Academia and industry have yet to even start on the assessment of senolytic treaments for more than three of four of those indications. Time is ticking. The world needs more organizations and collaborative projects like Lifespan.io and the RLE Group noted here, working to responsibly gather data to show whether the present range of promising approaches to the treatment of aging work or not.
Our another achievement is the plasmapheresis trial, which is pretty well-known in the community. We didn't expect to observe dramatic improvements in biomarkers that we would treat as promising, we just wanted to understand the logistics of the whole plasmapheresis process. Because you need to replace half of your plasma with the saline + albumin solution and this is not a simple and standard procedure. But we managed to calculate how many plasma you need to donate with each visit to the doctor and how many albumin you need to replace and we did this and surprisingly we have found some pretty interesting changes in the biomarkers of this gentleman. We have found, for instance and contrary to our expectations, that cholesterol goes both directions - bad LDL goes down and good HDL goes up, which is pretty interesting. Of course we have only two data points, so we cannot draw too many conclusions from that, but we have started a clinical trial aiming to compare plasmapheresis with albumin and without albumin, because the role of albumin of the whole procedure is an interesting question.
A few smaller things our group has achieved. We have tried various senolytics in our volunteers. Created a lentiviral vector for APO-A1 Milano gene delivery. And also a microbiome replacement experiment, because we have access to samples from soviet cosmonauts (who are usually considered exceptionally healthy, so our hypothesis is that transferring the microbiome could yield interesting health improvements).
Here are several things we are planning to deliver in the upcoming years. We are intrigued by the study showing muscular aging through 15-PGDH, and we want to reproduce it on ourselves. Another target is epigenetic rejuvenation of hematopoietic stem cell function via targeting Cdc42. This type of cell is very reluctant to different approaches in reversing aging (even our extracellular matrix one), so we plan to rejuvenate them and investigate how to maintain the useful environment for these rejuvenated cells. The third thing is targeting elastogenesis. Elastin is now considered to be one of the longest living proteins in our body, elastogenesis is limited to early infancy and then the old synthesized elastin remains in our body, accumulates calcium, is degraded by enzymes and so on, therefore we lose elastin which leads to progressive deterioration of various tissues - blood vessels, skin, lungs, ligaments, muscles, ... All tissues lose their elasticity and that is crucial not only for appearance but also functional health. We can try - and already have some methods - to increase elastin production in vivo.
These models are useful to support the average bio-hacker, but they really do nothing to move the rejuvenation industry forward.
They may provide some guidance for selecting some candidate to proceed with in formal therapeutic development, but those big millions of $$$ are still required to move the dial.
We cannot afford the industry to regress purely to this model or have the wider public believe it will be this simple
That's when the "crazies" take over completely
Hey @TimWillis,
I've always wondered why well known groups like Lifespan.io ARENT doing more trials. They've got the noteriety and clout... and it seems to me every time they want to raise money for a specific experiment, they do it pretty easily.
If the point of science is to find something that works a certain way, every time, then what does it matter if a little group does it or a big group does it? The Experiment and Data itself is what's important right?
What's the difference between a public drug company spending 25mil to get to phase 2 and Lifespan.io spending 250k for the same sort of information? Just a bigger sample size? More official peer review/oversight?
I don't ask these questions to be antagonistic... I'd just really like to know why things ARE the way they are (why is it taking so long to do a fisetin trial? etc.)
Thanks
@GREGORY S SCHULTE
I'm not saying they're bad to do
Just that they will mainly satisfy the small community of dedicated longevity people, bio-hackers, etc. who hang out at these blogs
But we need much more than that to entice the big money for the future
The Federal Death Agency (FDA) is a criminal and tyrannical agency which has NO right to exist. And it's KILLING us thru making health care so expensive. Too bad the longevity community has such a poor understandng of this issue.
@Gregory S Schulte - 250k is still a lot of money for lifespan.io to pony up at present, hopefully they can get more donations in the future.
Government regulation certainly does push costs way up. It is very hard to get right as although individual people in bureaucracies don't want to hold things up, they are not working in businesses competing in a free market where consumers are free to make choices. Without the threat of competition taking their business and then jobs away bureaucrats have no real incentive to control costs for the businesses they are regulating. Liberals propose setting up multiple regulatory agencies and letting them compete for business, and if necessary die from lack of winning any. But this is both politcally and practically difficult to achieve, mainly because the costs of not doing things are not visible to the public. No visible pain, no political interest.
A bit off topic but the article mentioned methods to ignite elastogensis in vivo. What are they?
@Gregory S Schulte - I can speak to your comments about Lifespan.io. While we would love to be able to fundraise and help launch more and more trials, it is not that simple. While we have raised considerable sums, it is by no means an easy feat. We are a small 501 non-profit and while we are doing our best to grow rapidly (we are taking on new staff right now in fact), we have not reached the point where it is trivial for us to raise the huge amounts needed for clinical trials.
That said, we are very interested in pushing the needle on projects similar to the PEARL rapamycin trial, so you can expect us to move that direction in the future.
We are also going to be launching our own research program in the near-future. I cannot say more at this point but we will be entering the research arena ourselves and more details will be published on our news outlet soon.