7 ms·

A once abandoned drug compound shows an ability to rebuild organs

132 points by LinuxBender 8y ago

ravroid 8y ago
Posting a paywalled article is pretty helpful /s
- nothanksmydude 8y ago
  What drug can I take to skip paywalls
- growingconcern 8y ago
  Can someone at least post the freaking name of the drug
dvno42 8y ago
Do you have a non-paywalled version of this?
- neonate 8y ago
  https://scientificamerican.express.pugpig.com/2019/03/13/a-drug-shows-an-astonishing-ability-to-regenerate-damaged-hearts-and-other-body-parts/ https://scientificamerican.express.pugpig.com/2019/03/13/a-d...
  - terrycody 8y ago
    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?
- StefanKarpinski 8y ago
  Related. I thought to myself “I used to read SA all the time, maybe I’ll subscribe, I wonder how much it is...” The price is $49.99 but the site refuses to tell you how often it’s billed. I can only guess that must be per year because, damn, that would be steep for a month. But really? You expect people to buy without knowing how often something is billed?
londons_explore 8y ago
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 8y ago
  Because it's super immoral? Everyone's fine with human casualties as long as they're not the ones doing the dying.
  - toomuchtodo 8y ago
    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 8y ago
      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 8y ago
        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.
radus 8y ago
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 8y ago
  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 8y ago
    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 8y ago
      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-florida-1/ https://orgprepdaily.wordpress.com/2017/08/21/breakin-bad-in...) 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-in-south-florida-5/ https://orgprepdaily.wordpress.com/2017/08/24/breaking-bad-i... 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.
matznerd 8y ago
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.00945.2010 https://www.physiology.org/doi/full/10.1152/japplphysiol.009... "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
pg_is_a_butt 8y ago
The best way to rebuild an organ is to break it down, and let the body respond. Maybe the original researchers knew about some unwanted damage it was causing, that might not show for years.
apo 8y ago
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 8y ago
  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 8y ago
    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.
- phkahler 8y ago

132 points by LinuxBender 8y ago

ravroid 8y ago

Posting a paywalled article is pretty helpful /s

nothanksmydude 8y ago
What drug can I take to skip paywalls
growingconcern 8y ago
Can someone at least post the freaking name of the drug

dvno42 8y ago

Do you have a non-paywalled version of this?

neonate 8y ago
https://scientificamerican.express.pugpig.com/2019/03/13/a-drug-shows-an-astonishing-ability-to-regenerate-damaged-hearts-and-other-body-parts/ https://scientificamerican.express.pugpig.com/2019/03/13/a-d...
- terrycody 8y ago
  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?
StefanKarpinski 8y ago
Related. I thought to myself “I used to read SA all the time, maybe I’ll subscribe, I wonder how much it is...” The price is $49.99 but the site refuses to tell you how often it’s billed. I can only guess that must be per year because, damn, that would be steep for a month. But really? You expect people to buy without knowing how often something is billed?

londons_explore 8y ago

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 8y ago
Because it's super immoral? Everyone's fine with human casualties as long as they're not the ones doing the dying.
- toomuchtodo 8y ago
  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 8y ago
    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 8y ago
      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.

radus 8y ago

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 8y ago
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 8y ago
  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 8y ago
    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-florida-1/ https://orgprepdaily.wordpress.com/2017/08/21/breakin-bad-in...) 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-in-south-florida-5/ https://orgprepdaily.wordpress.com/2017/08/24/breaking-bad-i... 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.

matznerd 8y ago

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.00945.2010 https://www.physiology.org/doi/full/10.1152/japplphysiol.009... "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

pg_is_a_butt 8y ago

The best way to rebuild an organ is to break it down, and let the body respond. Maybe the original researchers knew about some unwanted damage it was causing, that might not show for years.

apo 8y ago

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 8y ago
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 8y ago
  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.
phkahler 8y ago