There is a lot of discussion here about some rather exotic compounds or other treatments. While I generally recommend extreme caution with medication – I’ve seen plenty of people, not excluding myself, go off the deep end – I also don’t think mere access should be an insurmountable bottleneck. What have people here looked into, seriously or speculatively, but abandoned due to sourcing issues? Small molecules? Gene therapy? Just curious.
I have my own short list of things I can’t justify funding the manufacture/import/testing of myself, but I’ll leave this up for a while before adding anything further.
A while back I started researching for a book about aging. I was hoping to put together a guide of all of the most up to date treatments and compounds available. I may still finish it at some point. I was curious to see what the most cutting edge treatments might be available to the public, but I came to realize that despite the hype, there’s not really a lot of strong evidence for most of it. If you have enough money and you’re brave or reckless enough you can access it. This is probably fine if you have money to burn. I had seriously considered mesenchymal stem cells for a persistent joint injury and spoke the Stem Cell Institute in Panama, but the high price-25k tag put me off. I also looked into Exosomes, GDF11, Gene therapy and Plasmapheresis. The biggest barrier wasn’t so much sourcing materials as the cost. If you have 100k lying around you can have gene therapies for KIotho and Follistatin. Plasmapheresis costs about 5k per treatment, but one isn’t enough and it’s tell early to tell if it offers any long term benefits. Exosomes, which might have some promise you can find for about 7k a treatment, but then there’s the question of where they’ve been sourced from.
Yes, the real problem of course is that, even in animal models, nothing has been proven to work. Nonetheless, here are a few ideas:
Galactose conjugated navitoclax – Dasatinib is the only proven usable senolytic in humans, and even it has toxicity problems. Navitoclax has advantages but is far too toxic. Changing to the galactose prodrug should improve safety by a huge margin, probably at the cost of reduced central effect. The synthesis of this compound is published, but it is not available off the shelf.
Fasudil – Poking at the cytosketleton, and its interactions with the aging ecm – is an interesting strategy. Rejuvenation was recently demonstrated with CASIN, but that drug has no human safety data. Fasudil shows promise on several fronts and has a history of human use, but is not available in quantity.
Ibudilast – an interesting drug that used to be available from US vendors. Pharma product is available from Japan, with some difficulty and at high cost.
Thymus targeted FOXN1 fusion proteins, like demonstrated here. Regrowing the thymus is, IMO, essential, but the pathways are limited, so I’ll put this down as the most effective option, though I worry about immune response to the weird protein. Note that recombinant proteins are not an entirely turn-key tech, and so they are very expensive.
Yes, a few of those older arthritis drugs are interesting. Diacerein is another one. Salsalate is trivial to manufacture if you already do aspirin, for instance – I think that’s why it’s cheap.
Here’s one I haven’t found a good source for: Daprodustat. Roxadustat (in the same class) is available from at least one US reseller, and Desidustat may be source-able, but their longer half lives make me more cautious about safety.
Anyone who has an interest in this class drop me a note.
I know you’re in the UK, but in the US, it seems pretty cheap ($15 to $50 for a months’ supply) and available (though the issue will be getting a prescription)…
But it sounds interesting…
Conclusion
As shown in this review, salsalate therapy at the dose of 3 g to 4.5 g daily can lower insulin resistance and reduce the levels of glucose, triglycerides, and free fatty acid concentrations with minimal side effects. This inexpensive medication could be a useful option in the treatment of prediabetes. Larger clinical trials are needed, but the data are encouraging and should lay the foundation for further investigation and grant funding.
The most common availability issue is for the compounds that show some early positive results in research environments, and while obviously too early really for an evidence-based decision on whether to try or not, but some people are interested in trying. A number of compounds come to mind in this category: 17-alpha estradiol, ISRIB, IRISIN, …
In all these cases, the compound is relatively hard to get; you really need to have a friend at a lab who can order it for you (if you don’t work in a small lab or have a small biotech/chemical company).
I know it’s not a treatment or a compound, but I would really like a high sensitivity Sirolimus ELISA kit.
I’ve spoken to the company that produces them and sent them a couple of emails, and whilst they haven’t said no, I get the feeling they are just stonewalling me, in the hope I go away.
Atomoxetine
“Atomoxetine is a non-stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) in children, adolescents, and adults” (unlike Adderall which is a stimulant)
“Adderall generally has more frequent side effects compared to atomoxetine” (Though the studies directly comparing the two are quite limited)
My favorite supplier Jagish Nikose is not going to sell me any. That’s why I have other suppliers who are not squeamish about selling many products that Jagdish won’t supply
“Atomoxetine is not allowed to export from India as it is illegal medicine being a genuine company we don’t deal in illegal medicines.”
“Atomoxetine is not addictive. It has a very low potential for abuse and dependence.”
I don’t know what problem he has with Atomoxetine as its primary use is for ADHD not for depression etc. It does have a warning label about increased suicidal tendencies.
Apparently Daprodustat is available from Indian vendors, despite not being approved there, both as tablets for out of country consumption (namely Japan, I think) and as API. Not sure if the cost to verify these products is worth the potential gain in safety (which is just my guess, and hasn’t shown up in the clinic).
Thanks mate. I’m still sifting through the literature on hypoxia wrt aging, which is quite voluminous. A talk abstract showed up that might interest this crowd, for example:
Such things of course are very weak evidence in isolation. You can read a better review here. Not emphasized there is the fact that the integrity of stem cell niches requires hypoxic signalling. Anyways, overall picture is consistent with the common pattern of stress pathways becoming chronically activated but unresponsive with age.
If one chooses to induce brief burst of hypoxic signalling, there are a few options:
Use a device to lower the oxygen content of air while keeping CO_2 low. This is cheap and effective but I don’t particularly want to own a suicide machine.
Use breath control and rebreathing to lower O_2 saturation. This is very hard, though committed freedivers and some types of meditators can do it.
That leaves the pharmacological approaches. These drugs last for ~7 hours, which niavely seems too much, but digging into the safety reports Daprodostat (~3 hr) has more adverse effects then the longer-lived ones, so maybe I jumped the gun there.
Not to mention the beta subunits, or HIF-2 and 3. Anyways if you have any other ideas for poking at this thing that are at or close to the clinical stage, please do share!
I guess it’s a precursor in manufacturing or something ?
for that 