Alphabet's Calico has begun trials on a molecule for neurodegenerative diseases

ISRIB (the molecule discussed in the article) seems _very_ promising for brain health. But people who (recklessly?) self-experimented with it had strange cardiac issues. A study on dogs discovered heart anomalies. It’s nicely summarized here: https://forums.phoenixrising.me/threads/isrib-to-treat-me-cf...

"In the 1980s and 1990s, Walter demonstrated that when too many unfolded or misfolded proteins—which are characteristic of neurodegenerative diseases—were detected inside a cell, it triggered the equivalent of an emergency shutoff switch that halted all protein construction until the problem was solved. The action, which Walter dubbed the “unfolded protein response,” was akin to a blaring red alert at a busy worksite, stopping work; cellular repair crews would then converge on the site, attempt to fix the problem, and if all else failed, eventually order the cell to commit suicide."

So... if the body will naturally restart protein production when the problem is resolved, and if ISRIB forces it to restart without solving the problem...

Is this going to result in a few months of improved performance followed by a collapse as cells start dying for good?

No surprise, there's already a subreddit dedicated to people trying out this experimental molecule: https://reddit.com/r/isrib

The original article from which this is excerpted: https://www.technologyreview.com/2021/08/25/1031783/isrib-mo...

Honestly, the tone of this article is so hyperenthusiastic that it makes me skeptical. Calling something a "miracle molecule" and describing it as a potential panacea without strong evidence doesn't give me confidence; it sounds more like a sales pitch for a dietary supplement.

> the list of potential therapeutic applications for that molecule sounds almost too good to be true.

Maybe...because it is too good to be true?

edit: Apparently ISRIB is already being sold by various online vendors, much to the dismay of Walter himself: https://www.statnews.com/2016/09/28/memory-isrib-peter-walte...

Excerpts: "the molecule was licensed by Calico Labs, the Silicon Valley biotech established by the founders of Google to find drugs based on the biology of aging"

" In February, Calico announced that human safety trials had begun on the first drug candidate for neurodegenerative diseases it had developed based on the molecule, and that a study in ALS patients was slated to begin later this year. Other possible drugs for Parkinson’s disease and traumatic brain injury are likely to follow."

This is the molecule: https://en.wikipedia.org/wiki/ISRIB

This made me recall Nick Lane's thoughts on anti-oxidants and how they interfere with stress signals sent by cell (which is not an obviously good thing): https://nautil.us/issue/36/aging/yes-life-in-the-fast-lane-k...

Feel like I was just reading a comment on here today, in another thread, about how those stupid Google billionaires wasted all their money on this dumb Calico thing that will never amount to anything.

The interesting story here is why Calico would license the molecule whereas traditional pharma was not as interested. Age related incurable conditions are the happiest targets for blockbuster drugs. In all likelihood, someone with actual domain expertise would realize that there was already data which indicated the drug wouldn't make it to market. The team with the rights seized the moment of silicon valley longevity hype, and good for them.

Calico has a very strange pipeline of drugs that don't have much in common. The last paper about Yamamaca factors looked quite interesting, but Altos is much more focused on understanding just that one technology. Other successful new companies are platform companies, which Calico isn't.

According to the Huberman podcast, simply elevating your legs at night can improve the glymphatic system's ability to clear out junk from our brains. I haven't been able to find any links to actual studies on that though.

I can't complain about people doing medical research for good, but it's kinda strange that we live in a world where we can't have medical research unless online ads.

Excerpt : "The molecule has restored memory formation in mice months after traumatic brain injuries and shown potential in treating neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and Lou Gehrig’s disease (also known as amyotrophic lateral sclerosis, or ALS)."

"find it three times faster than mice that had received sham injections"

We are worried about placebo effects in mice now?

neurovegetative? is that what we’re doing now?

its like something I would say in my comedy skit before doing a Bill Burr style impression of someone on life support before insulting the audience for laughing. and then complain that everyone’s too sensitive.

I was a part of a group of people who obtained and took ISRIB a year ago. We made contact with another group from the Baltic’s who had a chemist in their ranks who had already synthesized and taken it, before we took delivery of ours.

The most important thing I learned is that you form a tolerance to it. At least that’s what the experiential effects indicated.

One person took it and developed heart rhythm problems.

Another person took it and became full of energy. Some people reported being much smarter and being able to socialize at a much higher level than before. Some people said they had hyper realistic dreams and compared it to schizophrenia. There were many stories but I can’t remember them all. I’m the end nobody took it long term.

The NMR results made it clear that everyone was taking pure ISRIB and not some adulterant.

One person said he gave it to his grandmother with Alzheimer’s and it made her better but she died shortly afterward. Some people said this is normal and it was a coincidence. We don’t know.

I never took it because right before we had secured a supplier I had a bad reaction to another experimental drug which has given me a permanent injury.

I think you mean neurodegenerative diseases, not neurovegetative?

Jaw dropping molecule supremacy breakthrough

I'm curious why it is referred to as "molecule" everywhere. It may be a molecule, but...so is everything else. This is the first time I have seen this term used to describe a drug or treatment.