
A once abandoned drug compound shows an ability to rebuild organs - LinuxBender
https://www.scientificamerican.com/article/a-drug-shows-an-astonishing-ability-to-regenerate-damaged-hearts-and-other-body-parts/
======
apo
I'm going to throw this out there not knowing much about the specifics in this
case. Academic biologists suffer from tunnel vision when it comes to
developing drugs.

Here's a script I've seen play out way too often. Molecule exhibits
interesting behavior. Molecule is examined more closely in vitro and in vivo.
Effects appear to be for real. More studies are done. Years go by.

And at no time was a single close analog made. Nor was a medicinal chemist
ever consulted. Little to no structure-activity relationships were performed.
The molecular mechanism of action remains mostly unknown as a result.

The thinking seems to be that drugs are discovered (by biologists), not
developed (as in software through an iterative process). Some drugs are
discovered, but most are developed.

The compound that biologists are interested in right now isn't the good part.
The good part is the underlying mechanism and how amenable it will be to
actual drug development.

~~~
sametmax
Making the mechanism of action known open the door to alternatives and
competition. If a firm pour millions into a project, they want exclusivity. In
our current system it's more important than good science or choosing what's
best for humanity.

~~~
thereisnospork
But for the academics their prestige rests on publishing that mechanism of
action. Determining x drug works via inhibiting such-and-such transferase via
pi-pi interactions (for example) is how careers are made, and in cases where
the learning is important enough to shutter away, typically the academic will
license it out or go into business for themselves -- which is just fine
because that means we get a drug out of it, if there was one to be had.

The problem is that the academic side isn't generally focused on things that
matter about getting a drug to market(e.g. what happens when you swallow it?
Does inhibiting such-and-such transferase actually do anything meaningful?
What does it metabolize into? etc.) Lots more glitz and glamor (and lots
cheaper) to make a compound inhibit something or kill cancer in a petri dish.

Its vaguely as if say computer science academics were studying code golf.

------
matznerd
Most pertinent quote here is that the only reason it was not pursued was
because it is not orally bioavailable:

"But because the drug comes as a liquid that needs to be injected every day,
it was unlikely to be popular with patients who already had alternatives, such
as pills, that were easier to take. Pharmaceutical companies did not pursue
it."

There are many other molecules out there that have advanced properties but
have difficult delivery methods, including some nootropics (semax, selank,
cerebrolysin, etc).

There is a group though that has no problem injecting things into themselves:
bodybuilders and athletes. Fortunately for us, they have brought some other
abandoned molecules back from the dead, mostly ones that heal injuries.

For example, there is a molecule found in human gastric juices, known as Body
Protecting Compound 157 (BPC-157). Part of the intestinal lining has to
regenerate itself nearly weekly. This compound, isolated from there, and then
synthesized, is used prolifically by athletes/bodybuilders with
tendon/ligament injuries, but can also be used for repairing stomach issues.
etc. It is widely available on the internet. Here is the science for you:

"As has been demonstrated for many organoprotective agents using different
models of various tissue lesions, despite the poorly understood final
mechanism, practically all organ systems appear to benefit from BPC activity.
These effects have been achieved in many species using very low dosages
(mostly microgram and ng/kg range) after ip, ig, and intramucosal (local)
application. The effect was apparent already after one application. Long
lasting activity was also demonstrated. BPC was highly effective when applied
simultaneously with noxious agents or in already pathological, as well as
chronical, conditions. Therefore, it seems that BPC treatment does not share
any of the so far known limitations for 'conventional organoprotectors'. No
influence on different basal parameters and no toxicity were observed. These
findings provide a breakthrough in stress theory. BPC, as a possible
endogenous free radical scavenger and organoprotection mediator, could be a
useful prototype of a new class of drugs, organoprotective agents."
[https://www.ncbi.nlm.nih.gov/pubmed/8298609](https://www.ncbi.nlm.nih.gov/pubmed/8298609)

"Pentadecapeptide BPC 157, composed of 15 amino acids, is a partial sequence
of body protection compound (BPC) that is discovered in and isolated from
human gastric juice. Experimentally it has been demonstrated to accelerate the
healing of many different wounds, including transected rat Achilles tendon.
This study was designed to investigate the potential mechanism of BPC 157 to
enhance healing of injured tendon."
[https://www.physiology.org/doi/full/10.1152/japplphysiol.009...](https://www.physiology.org/doi/full/10.1152/japplphysiol.00945.2010)

"BPC 157 may serve as a novel mediator of Robert’s cytoprotection, involved in
maintaining of GI mucosa integrity, with no toxic effect. BPC 157 was
successful in the therapy of GI tract, periodontitis, liver and pancreas
lesions, and in the healing of various tissues and wounds."
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333585/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333585/)

" A novel stomach pentadecapeptide, BPC-157, improves wound and fracture
healing in rats in addition to having an angiogenic effect. Therefore, in the
present study, using a segmental osteoperiosteal bone defect (0.8 cm, in the
middle of the left radius) that remained incompletely healed in all control
rabbits for 6 weeks (assessed in 2 week intervals), pentadecapeptide BPC-157
was further studied (either percutaneously given locally [10 microg/kg body
weight] into the bone defect, or applied intramuscularly [intermittently, at
postoperative days 7, 9, 14, and 16 at 10 microg/kg body weight] or
continuously [once per day, postoperative days 7-21 at 10 microg or 10 ng/kg
body weight])...Pentadecapeptide BPC-157 significantly improved the healing of
segmental bone defects."
[https://www.ncbi.nlm.nih.gov/pubmed/10071911](https://www.ncbi.nlm.nih.gov/pubmed/10071911)

"BPC 157 improved muscle healing, macroscopically (less hematoma and edema, no
post-injury leg contracture), microscopically, functionally, and also based on
enzyme activity (creatine kinase, lactate dehydrogenase, aspartate
aminotransferase, alanine aminotransferase)...BPC 157, at all investigated
intervals, given locally or intraperitoneally, accelerated post-injury muscle
healing and also helped to restore the full function."
[https://www.ncbi.nlm.nih.gov/pubmed/18668315](https://www.ncbi.nlm.nih.gov/pubmed/18668315)

~~~
amelius
I wonder, though, what the downsides are of this drug. If the human body can
produce it and if there are only upsides, then why didn't evolution make the
substance more abundantly available?

~~~
entee
Things that cause growth are generally a very bad thing in biology, because
they cause cancer. Look at a list of proteins key to cancer and you'll find
tons of growth promoters, some of which have the word "growth" right there in
the name (the G in EGFR, FGFR, VEGFR, IGFR).

Growth must be tightly regulated to not end up as cancer, so that's why it's
not abundantly available.

~~~
gotocake
The article makes the point that despite human trials originally, and later
one-cell zebrafish embryo tests, no sign of carcinogenesis was detected. They
further explain that given its limited range within the body, it only
impacting damaged tissue and the short period of time it would be used, it’s
unlikely to be carcinogenic.

~~~
entee
Oh sure, this agrees with the "tightly regulated" constraint. Short time,
localized application/expression qualify. I'm not sure that long term exposure
would be good, and in reference to BPC-157 let's not forget that intestinal
cancers do occur (though I'm not at all sure if there's ever been a link
between BPC-157 and intestinal cancer).

It's great that the compound looks safe given the limited amount of
information we have, but it sounds like there's not a whole lot of trials out
there with the power to test the possibility that this could be cancerous long
term. Happy to be proven wrong though!

~~~
gotocake
Remember the initial human trials were using it systemically to control blood
sugar, and specifically looked for carcinogenesis. Obviously there’s room for
something to have been overlooked, but in the narrow case of this particular
molecule I’d be hopeful. As for BPC-157 we’re very much on the same page, and
I’d be very concerned about cancer.

~~~
entee
Oh interesting, I'd missed that. Thanks for the note!

------
dvno42
Do you have a non-paywalled version of this?

~~~
neonate
[https://scientificamerican.express.pugpig.com/2019/03/13/a-d...](https://scientificamerican.express.pugpig.com/2019/03/13/a-drug-
shows-an-astonishing-ability-to-regenerate-damaged-hearts-and-other-body-
parts/)

~~~
terrycody
good site, is it paid? I mean, you have to pay for this website and you can
enter the entrance of next posts? I try to find some clickable places, but
can't find any. But why we can visit free like this URL?

------
radus
Relevant study in zebrafish/mice with this compound (MSI-1436, aka
trodusquemine):
[https://www.nature.com/articles/s41536-017-0008-1](https://www.nature.com/articles/s41536-017-0008-1).

~~~
HarryHirsch
The compound looks like a detergent, something that would insert into cell
membranes and disrupt them. Saying that it inhibits this or that kinase is
really a long stretch.

~~~
radus
I think that's a bit of a harsh dismissal. It's a sterol natural product that
binds to PTPN1 allosterically. I've scanned the literature a bit and it seems
reasonably well validated. It's termed as selective in many papers, but this
is primarily referring to selectivity over a PTPN1 homolog, something which
previous compounds had had trouble with.

~~~
HarryHirsch
I once worked for someone who had no clue about biology and had no critical
faculties at all. She was like "but it inhibits target X", and you'd go like
"and God know what else" because the compound looked far too much like a
promiscuous binder. Then she'd tell you you were a pessimist. She had an
Elizabeth Holmes portrait in her office until late 2016.

It was a complete shitshow, like the experience of the guy behind Org Prep
Daily at his startup (starts here:
[https://orgprepdaily.wordpress.com/2017/08/21/breakin-bad-
in...](https://orgprepdaily.wordpress.com/2017/08/21/breakin-bad-in-
florida-1/)) minus the drug manufacturing, although I'm positive that the
bosslady was on stimulants. After such an experience you get skittish.

Elsethread someone mentioned a supposedly copper-binding orally active
derivative. Copper-binding in stomach acid? How much of that has been
validated? Part 5 of "Breaking Bad in South Florida" might be relevant:
[https://orgprepdaily.wordpress.com/2017/08/24/breaking-
bad-i...](https://orgprepdaily.wordpress.com/2017/08/24/breaking-bad-in-south-
florida-5/)

David Lowe has something about supposedly selective compounds polluting the
literature, but I can't fidn the blogpost right now. I agree with his
sentiments.

------
ravroid
Posting a paywalled article is pretty helpful /s

~~~
growingconcern
Can someone at least post the freaking name of the drug

------
londons_explore
If this drug has a 98% chance of having no effect, 1% chance of preventing
heart disease, and a 1% chance of immediately killing me, it's still in the
interests of someone with heart disease to take it.

It's definitely in the interests of humanity as a whole - a few hundred people
might be killed in the cavalier hunt for effective drugs, but tens of millions
every year will be saved.

Why are so many years of studies/paperwork needed? Why not just produce the
drug and let people take it (who know the above risks)? That could happen as
soon as this afternoon.

That wouldn't be a proper blinded study, but the results of it would be very
strong indications for if the drug should go through the full process to
become a standard treatment.

~~~
notfromhere
Because it's super immoral?

Everyone's fine with human casualties as long as they're not the ones doing
the dying.

~~~
toomuchtodo
I’m a responsible adult who believes in personal responsibility. Provide the
data around efficacy and risk, and allow me to make the informed choice
myself.

I am okay dying if I make a mistake in my risk assessment. I would not make
the choice for someone else.

Everyone dies. Progress is inherently risky, but necessary.

~~~
bradknowles
So long the "informed consent" really is truly informed, and not something
that is slanted or otherwise concealing evidence or data. In that case, then I
do not disagree with you.

However, considering what we know of how PR and Marketing works, I am inclined
to err on the side of "Abundance of Caution and Due Diligence", even in the
face of personal responsibility.

~~~
toomuchtodo
Definitely. Making the marketing of pharmaceuticals directly to consumers
illegal would go a long way, as well as stronger oversight and governance by
regulatory bodies.

