Minicircle: This biohacking company is using a crypto city to test controversial gene therapies (MIT Tech Rev)

#1

We’ve discussed Minicircle, the Roatan, Honduras based startup that is doing private gene therapy (and other) clinical trials for longevity, etc. See these past discussions:
Here: Follistatin injections via Minicircle plasmids? They're recruiting new volunteers for trials in Honduras
Here: Longevity Clinics: What They Are, Services & More
Here: Edit Human DNA at Home With a DIY CRISPR Kit

If anyone visiting our site has participated in any of these trials at Minicircle, please post information about your experiences and outcomes.

Now the MIT Technology Review is covering them in this new article:

The advertisement—posted on Mirror, a Web3 publishing platform, in March last year—outlined an eye-catching if perhaps confusing proposal: “Access NFTs for a follistatin plasmid phase I clinical trial in Prospera ZEDE, Honduras.”

The ad had been posted by a biotech startup called Minicircle, which was recruiting participants for a clinical trial of gene therapy. But several details made it unusual. For one, it instructed would-be guinea pigs to purchase an NFT to take part. Upon completing the study, it promised, they would receive payment in cryptocurrency. And while it notes the geographical location of the trial, test subjects may not have immediately understood that it would get underway in what is essentially an experimental crypto city—Próspera, Honduras.

The unconventional recruitment effort marked a curious development in the space of gene therapy, a cutting-edge field that has endured decades of false starts and setbacks. FDA-approved gene therapy treatments remain rare, but those breaking through come with eye-watering price tags, in part because of the cost and complexity involved in their creation.

Full article here:

2020 Podcast Interview with the Founder of Minicircle: Mac Davis:

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#2

I did see this comment from someone who has participated in the minicircle therapies:

A bunch of folks have asked me for details about the follistatin therapy I did with Minicircle in October.

Last I heard, they were still looking for participants for the next cohort in January, so here’s some info for anyone who wants to participate.

  • The webpage for this therapy is Our Therapies - Minicircle
  • It’s basically injecting little circles of DNA into your fat cells, which then produce follistatin that enters your bloodstream.
  • It’s free, except for the cost of flying to Roatan (off the coast of Honduras), and the hotel.
  • The procedure is done at the GARM Clinic https://garmclinic.com
  • It’s a very quick (10-20 second) and relatively painless injection.
  • It apparently increases circulating follistatin levels to around 22 ng/mL – around the level of a teenager, but far less than a pregnant woman or a newborn, which is around 55-60.
  • And while follistatin does inhibit GDF11 due to the similarity between GDF11 and myostatin (aka GDF8), my best guess is that this level is probably not high enough to significantly reduce GDF11 levels. And you can always order GDF11 from CanLab, or join Steve Perry’s study, if you’re worried about that.
  • It’s temporary (lasts 18 months), and it even has a built-in kill switch so you can instantly reverse it with tetracycline or doxycycline.
  • They reported around 3.5 pounds of muscle mass gain and 3.5 pounds of fat loss for the average participant so far.
  • It also requires monthly DEXA scans and blood tests for a few months before and after participation.
  • If interested in being part of January’s cohort, email coordinator@minicircle.clinic and tell them I sent you.

If you end up participating, be aware that although the resort they suggest (Las Verandas https://www.lasverandasroatan.com) is quite beautiful, it has no amenities besides a small beach and a few pools (no fitness room and no place to buy goods, and the nearest supermarket really requires a taxi to reach), and I personally found most of the rest of the island a bit on the sketchy side.

So unless you enjoy just chilling by the pool (and have a significant other to hang out with), I recommend making your trip as short as you can – I ended up wishing I’d just flown in the day before and left the day after.

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#3

I’m glad others are trying this, but safety concerns don’t make me want to be an early adopter. I would love to hear any stories about using the clinic.

#4

You can always address safety concerns with more testing (and they do partner you up with SOME testing).

The minicircle founders are SO GREAT because they don’t have the fucking hangups that everyone else has. We need to get through these damn hangups if we want to make ANY progress, and N=1 self-experimentation now is WAY safer than it was 60 years ago when it wasn’t as stigmatized. You need “people willing to try anything” for the general social good, you even need bodybuilders who inject anabolic steroids into themselves for “the social good”

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#5

Related -

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#6

Reason is a long-time and strong proponent of “radical longevity” similar in approach to Aubrey De Grey, and a local SF Bay Area resident. He hosts the website Fighting Aging (and I recommend his regular newsletter on aging). I’ve heard he is an avid and early adopter of new longevity technologies, including senolytics (dasatinib, etc.) and now Minicircle’s gene therapies…

Below is Reason’s response, to the MIT Tech Review article from above:

Minicircle is working towards the upregulation of follistatin, an inhibitor of myostatin and thus an interesting target for improved muscle growth and treatment of sarcopenia. Follistatin and myostatin are well studied genes in this context, and there are any number of animal studies, as well as human trials of various approaches to myostatin inhibition. As I have long said, follistatin and myostatin are probably the most compelling, least risky genes to start working on if interested in gene therapy development. There is a great deal of animal and human data to support this work.

It is always annoying to see shabbily written popular science articles in which ignorance is brandished with a sort of pride. The author of today’s article couldn’t get Minicircle to comment on the details of their work, has no real idea as to what is going on under the hood, and so forges ahead with a mix of snark and commentary from various people who also don’t know what Minicircle is doing, or the nature of their gene therapy approach.

I am a participant in the Minicircle follistatin trial. I’ve also signed a non-disclosure agreement, so don’t ask me for details. The company has an interesting, novel technology for the delivery of gene therapies, and is undertaking a responsible, low-cost, first-in-human clinical trial outside the US with educated volunteer participants from the self-experimentation community. It consistently amazes me, the degree to which hostility is poured upon those who choose not to engage with the journalistic and regulatory priesthoods in exactly the approved fashion.

The present system of regulation, and the enormous costs it imposes on development and discovery, must change. We live in an era in which a prototype gene therapy can be safely assembled for a few thousand dollars in cost of goods. It cannot continue to be the case that development only progresses at a cost of tens of millions of dollars to reach initial human trials, and hundreds of millions to billions of dollars to allow the average person to be permitted to use a treatment.

And, just to be balanced here, below is the opinion of Christin Glorioso, the Founder/Leader of the San Francisco Longevity (now Global Longevity) Groups, and the founder of NeuroAge Therapeutics (an Alzheimer’s targeted startup in San Francisco). She probably accurately represents a significant number, (not sure if its most) of the San Francisco Longevity Startup / Biotech founders views and fears on this area… they are very concerned that their Biotech efforts / funding may be harmed if something goes bad in these types of Longevity Hacker efforts.

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#7

My main concern is that delivery of the vectors is rather random and it gets into all sorts of cells (causing increased mosaicism). If it’s the type of mosaicism that matters - I don’t know. It’s probably less risky than what Liz Parrish did with AAV. I know other people (eg Ring Therapeutics) are working on non-AAV viral vectors

I know they use a “kill switch” to reduce risk, but will the “kill switch” still work if some of the transfected cells become less accessible over time? (eg through mitosis). I know delivery of the vector is harder than delivery of the “kill switch”

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#8

“but will the “kill switch” still work if some of the transfected cells become less accessible over time?”

What tissues are you concerned of being inaccessible to *cycline antibiotics?

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#9

I participated in the trial. I put on 15 pounds in 3 months and 8 pounds of it was lean mass. I’m 5 months or so out and still bulky. I did feel a drop compared to the first few months of the treatment, but I still am carrying substantially more muscle. The shit works boys and girls. MIT ‘tech review’ be damned lol

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#10

Welcome to the forums! Can you share a little more details on your experience with the follistatin therapy. Was it a single injection or a series of them? Was it done intramuscularly, or some other avenue of delivery? Any side effects noticed at all?

Its great to hear from someone going through the trial.

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#11

They could market it not just for aging/disease, but for more general sleep reduction/“enhancement” (eg bodybuilders, intelligence enhancement in AI researchers for the sake of increasing AI interpretability, which becomes way more important in the case of “short timelines” => making humans smarter can help reduce risk). The point about AI researchers I actually brought up to one person who understands (I even link it to this thread) => AI alignment people scared of p(doom) are pretty much willing to get over hangups others aren’t.

[fwiw maybe AI alignment is not the most important thing and many of them are too technophobic to be “net positive”, but still, there are enough of them who are open and they are at least nice/accessible and have access to “sense of urgency resources” and I’m friends with A LOT of them so they are at least “socially important enough”. And theoretically there is a small pool of them who may be more “convinced to bewilling to try anything” than almost anyone else - BOTH physically and ontologically given that is the only way to guarantee them an increased chance against what seems to be “near certain death”]

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#12

=> This is more easily tractable than increasing intelligence, and we do have a gene for it. This could be important for those with super-short timelines

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#13

Its interesting… if we insert the gene for less sleep requirement, that is effectively like increasing your lifespan, because you can get your required work done more in the time when you would have been sleeping, thus opening up time during the day for more social and other activities… so a 25% sleep reduction hack, is almost like increasing your lifespan by 25%.

#14

If you put on 7 lbs of non-lean-mass, that’s very concerning. How did your % fat mass change before and after? Abdominal fat?

How much can you bench-press/lift before/after?

#15

I’ll have to go back to the DEXA scans and confirm the breakdown of the non-lean weight gain, but I don’t find it concerning as my weight historically fluctuates a great deal w respect to my water weight, especially if I have more muscle on my body. I don’t do lifts for strength and pretty much exclusively train for combat sports, so I don’t have those numbers.

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#16

Single injection into abdominal fat. And thanks yeah it’s pretty damn cool to have had the honor of doing it.

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#17

More here: Follistatin injections via Minicircle plasmids? They're recruiting new volunteers for trials in Honduras - #6 by AlexKChen

They plan to run a fitness study next (eg compare values pre and post benchpress). See

Running a fitness study is another type of study and requires a fitness lab to verify that correct form and numbers are established during the movement — logistically it’s best suited to recruit patients all from nearby the same fitness lab.

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#18

Can you please share more about your experience. This is really interesting, I think, for many of the people here. When did you go to Roatan to participate in the trial? Is this something people have to pay for? if so, how much? How long does the process take, what is involved other than just the single injection? It sounds like it could be quite quick. Do they want you to say on the island for a few days afterwards for medical monitoring, or did you leave immediately afterward? How quickly did you start to notice effects? Any side effects?

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#19

I remember going down the FST rabbit hole and reading that it can increase muscle mass but not correspondingly increase strength

Muscle mass is much more conserved with age than muscle strength - not convinced yet that FST will be that helpful for aging w/o more data

#20

“Can you please share more about your experience.”

Sure, no problem. Just have to be brief and specific as some things are NDA.

“When did you go to Roatan to participate in the trial?”

We went to a beautiful resort out there.

“Is this something people have to pay for?”

You are expected to pay for blood tests, but that is it.

“How long does the process take, what is involved other than just the single injection?”

You have an intake interview and a consultation with the Doctor. They ask you some questions and then it’s stabby jabby time. By that time there has already been a bit of a selection process and conversations with the team. Very quick process as far as the operation itself. They’ll typically have you wait around or be nearby in the immediate term in case some random very unlikely unforeseen catastrophe occurs.

“Do they want you to say on the island for a few days afterwards for medical monitoring, or did you leave immediately afterward?”

Yes, they are very careful about that and want you to remain on the island a few days.

“How quickly did you start to notice effects? Any side effects?”

I feel like maybe on the 5th or 6th day I just started to notice a little bit more of a pep in my step. By the fifth week I was noticing substantial morphological changes in my muscle mass and endurance during jiutjitsu/MMA practices. I believe the effects had a ‘peak’ somewhere around 8 weeks, but I am still currently holding muscle mass that I did not have previously.

In regards to side effects, I would say that there is a small potential that my body in the initial stages may have had some slight nerve pain due to increased muscle mass in my neck area? However, I put my body through a great deal of abuse and high-volume high-impact damage with combat sports and I have a myriad of injuries that I collect each year, so it could 100% easily be nothing. I did notice an increase in appetite both sexually and food-wise. I didn’t experience much psychological change other than indirectly being excited about the fact that the experiment was actually working, but psychological changes are difficult for me to measure or understand (even if all I did was drink a cup of coffee). I still do carry more muscle mass and I am a bit stronger. During the trial, I was not lifting weights or making any changes to my training regimen as I wanted to be sure that something was happening. I am telling you 100%, something is definitely happening in those cells.

Is this an instant GMO Hulk-a-mania science juice? No it is not… but is it actually working and doing something? Oh hell yeah it is.

I would urge people who are interested in providing lukewarm opinion or shallow tepid recoil to this project (especially press) to actually interview people who’ve undergone these processes rather than simply dismiss it.

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