Wanted: A Non-Profit to Run as Many Low-Cost Trials of Promising Treatments for Aging as Possible
A major gap exists in the present spectrum of efforts to develop the means to treat aging, rejuvenate the old, and turn back age-related conditions. An the one hand, a small number of promising potential therapies to treat the mechanisms of aging can at present be applied by physicians off-label, or otherwise without the need for a great deal of interaction with the FDA. On the other hand, there are a good hundred or more clinical indications, specific age-related conditions recognized by regulatory authorities, that might be improved by these therapies. Several hundred small, informal trials could be run, starting now, given approaches that presently exist, in order to determine whether or not these forms of therapy are in fact effective.
Let us only consider the senolytic combination of dasatinib and quercetin, for example, a low-cost treatment that can be given off-label and that has been demonstrated to clear senescent cells in human patients. Clearance of senescent cells in mice produces profound and rapid rejuvenation. Senolytics as a class of therapy are at present in human trials for only a few indications: osteoarthritis, idiopathic pulmonary fibrosis, COVID-19, chronic kidney disease, and recently Alzheimer's disease. The whole senolytic industry, and associated academic trial groups, after nearly ten years of development, has done no more than initiate a few formal human trials, at great expense, and which are very slow to answer the question of whether this actually works well. Senescent cells are involved in some way in near every age-related condition, disrupting tissue function throughout the body, provoking chronic inflammation. Effects on the full panoply of age-related conditions could be assessed. This is not being done.
If considering small informal trials, let us say that one aims for 100 to 200 people per trial, more than enough to produce meaningful evidence for efficacy when the effect size is significant. With volunteer efforts, cheap off-label treatments and low-cost assays for suitable endpoints, this sort of informal trial can be conducted for $200,000 - which is exactly what Lifespan.io is doing for their PEARL trial of mTOR inhibition. The model works. Even if the cost were $500,000 or $1,000,000, then that would still be vastly cheaper than the full, formal FDA IND process. A single non-profit with significant funding could run many such trials in a year, generating human evidence at a much greater rate than the scientific community and biotech industry combined are managing at the moment.
That evidence is much needed. There is an enormous amount of funding sitting on the sidelines. Funding that could be supporting the deployment of senolytic drugs to the population, or could be running large-scale formal clinical trials to validate the use of senolytics. The organizations capable of deploying that funding are very conservative. They will only start in on such project after there is already proof, after the debate is already won. Which is why we need the results of many low-cost trials - in order demonstrate that dasatinib and quercetin is a meaningful and useful approach to the treatment of aging.
Everything said above about the dasatinib and quercetin senolytic combination also applies to, say: fecal microbiota transplantation; or periodic blood plasma dilution; or the Khavinson peptides for thymic regrowth; or the Intervene Immune approach to thymic regrowth; or CASIN for CDC42 inhibition and restored immune function; or injection of stem cell derived exosomes; and forth into a growing list of approaches that may well be capable of achieving good results in old people. Many of these are already being used by self-experimenters, but that will never generate the sort of data that is convincing to the powers that be. There is tremendous potential to demonstrate benefits in older individuals via addressing one or more of the underlying mechanisms of aging, and the world is instead largely squandering time as the clock keeps on ticking on all of our lives.
It is all true. However, let's not forget that even a single failure of such approach might give bad reputation to the field and set it back a decade or even two. So we want to be more efficient but not to cut safety and predictability corners.
I guess taking fisetin for joint paint is a low risk approach. Having a study of D+Q for back-pain is another story.
One off-label but not far away would be using D+Q after a round of chemo or radiation treatment. It might enhance cancel killing and reduce the bad effects of the initial therapy. This one sounds low risk to me.
Many low-cost anti-aging human trials combined together would still cost millions of dollars.
If one informal trial costs $100,000 and non-profit org does 50 different trials per year , then it will cost $5million per year . It would need an annual budget of $5million per year. Such organization can not start trials until it fund raises $5,000,000. Most trials will be unsuccessful, if it is 20% success rate - it will still be a progress toward curing aging.
And because successful treatments will not be FDA approved - patients can be treated in countries and islands where government approval is not required - medical tourism.
But Still
Will there be enough human volunteers or recruits at low cost to make trials effective.?
This may be an opportunity for Doctor Aubrey deGrey to start such non-profit organization, if he is no longer working at SENS Research Foundation.
@Nicholas D
There are enough old people. Some trials for be done for cheap(ish) like senolytics or rapamycin for , say back pain. But others will require more expensive setups. Of one uses creative meta-analysis piggyback on an existing trial with an extra protocol they're could be done extra savings. But if we want to test something more advanced likes personalized immune therapy or cultured stem cells the cost well climb up quickly.
https://www.nature.com/articles/s41421-021-00268-z
The SARS-CoV-2 protein ORF3a inhibits fusion of autophagosomes with lysosomes
(and thus inhibits autophagy)
I wonder is this a general thing with viruses?
May explain why we age as the immune system fails.
Gotta do it
Other wise you get charletans like this running the show - https://www.youtube.com/watch?v=ScJNE0alsaQ
Why are Bioviva charlatans Chuck? They are running non-FDA trials of potential anti aging treatments like telomerase and klotho - things that have been shown to be beneficial in mice. Admittedly it is gene therapy, so not exactly low cost, but this sounds like the kind of thing Reason is suggesting (Bioviva are for profit, but the recent gene therapy for Alzheimer's was charity funded).
I love this idea.
I have no idea what is involved in establishing a foundation or, more importantly, in attracting donations of sufficient size to keep this up. Would donors lose interest after funding 1 or 2 trials per year? I have assumed that is one of the reasons LEAF doesn't do more frequent trials although Steve said in a previous post on this subject that it still isn't trivial for them to do this, which I took to mean at a personnel level. So, perhaps with a foundation devoted to this, with appropriate structure, oversight, directors, advisors, etc., the money would come?
I have no idea if this would fit in with your plans, but I have a 501 (c) (3) that I use to provide medical care in the form of kidney dialysis for young adults in Ukraine. It is a personal philanthropic effort of my own, but the foundation could provide the framework for the charitable foundation portion needed to execute your plans. I currently live in Tbilisi, Georgia close to the medical school. I am a retired MD and a Fellow in the American Academy of Orthopedic Surgery. If there were to be interest, I could make contact with the faculty of the medical school here and trials could be performed here in Georgia. English is the major academic language used, so medical staff in the US should not have a great deal of trouble communicating with compatriots here. Regulatory oversight is present, but not nearly as strict as in the USA. If anyone is interested, I can be contacted at the listed email address and options for research and proper audited management of a potential project can be discussed.
One additional note. I personally know one off the writers of personal interest articles for the local newspaper here in Tbilisi. Tbilisi is a city of 1.5 million in a country of 4 million people. We could have a very good public relations campaign to get things started.
We can do trials in non-EU, non-US countries where there's no such strict regulation and people are getting paid less for the trials, so it's even less than 100K for non-FDA approved research. We got many private labs in Russia to do the job.
Let's organize this
I am interested in helping a not for profit as described here. I have some experience in fundraising once the trials have been designed and there is a business plan I can take to potential donors.
I like this idea but would like to expand on the idea...
It seems that there could be two levels of the "Fast, small micro clinical trials" that you have proposed.
1. When good academic studies come out on life extension in mammals - like the NIA ITP studies on rapamycin, canagliflozin, acarbose, alpha-17 estradiol, etc. it immediately stimulates interest and activity in the enthusiast community. People start talking with their doctors and doctors start prescribing these medications off label if the side effect profile looks reasonable.
2. As a precursor to your micro clinical trials (which I completely agree with) why not also have an earlier program that starts right after the new compelling new compound comes out. People begin using these compounds quite quickly these days - so lets start gathering the data and sharing it with researchers (and ultimately with the FDA to help get them on board) to move things forward faster.
I've recently started a new website in part to help achieve this.
https://www.rapamycin.news
This is a new site focused on helping people who are early adopters of new anti-aging drugs, to help gather information on using these drugs, to gather information on the benefits and side effects of these drugs, and to share information with researchers and other groups to help move the science forward faster.
I've worked in biotech / digital health in the SF Bay Area for the past two decades and the FDA highly values real world experience these days - what does the drug actually mean to the patient in terms of benefits and side effects on a daily basis. At our site users are encouraged to share the information and tack that information in their user profile. Over time - I think we can have a pretty good database of information on these new drugs and how they are affecting people. This could be the basis for studies done by academics (we're talking with a number of them right now) that can help translate this into publishable, quantifiable results that could then drive the mini clinical trials that you are envisioning.
I forgot to add a link to the FDA's page on Real World Evidence. I think this is how we help get the FDA over to the side of being more accepting of aging as a target for pharmaceuticals:
https://www.fda.gov/science-research/science-and-research-special-topics/real-world-evidence
My vote for urgently needed initiative is to get a well-designed trial of plasmapheresis underway stat. I met with Dobri Kiprov last week, and he's using plasma exchange to treat Alzheimer's and several autoimmune conditions. There are plenty of interested participants, but running a dozen plasmapheresis sessions costs around $50K, a fair chunk of change that would deter most people. Given the neutral blood exchange results in mice from the Conboy lab and the AMBAR study for Alzheimer's, I think there's a fantastic opportunity that's just sitting there because we aren't getting sufficient data in trials to prove the efficacy.
We'll give people a $100K/year placebo called aducanumab, but plasmapheresis, a cost competitive approach that might actually work, gets no attention because it lacks a multi-billion dollar pharma marketing machine. This isn't a cheap study - probably needs $10-20M - but it's cheap relative to anything the industry is running. It won't get run, though, because the therapy is pretty much public domain...