Why PMX-30063 will revolutinize?

Conventional antibiotics generally must enter the bacterial cell to
interact with their biochemical target. Bacteria generally can
develop resistance one of two ways:
• Efflux --- pump out the foreign chemical which has crossed
through the cell membrane; or
• Target mutation --- because of rapid reproduction, bacteria
change the structure of the biochemical target

PMX-30063 mimics host defense proteins in that it does not
have to enter the cell. It directly disrupts the bacterial cell membrane
from the outside - sidestepping bacteria’s own resistance
methods (efflux and target mutation) - which makes bacterial
resistance unlikely to develop.

Source: http://irgnews.com/sites/default/themes/publisher/images/companies/PYMX/PYMX_fs.pdf

Bacterial resistance to the PMX molecules by Falconer66a

Frankly, the PolyMedix PMX molecules are simply resistance proof. In order for a bacterium to gain resistance it would have to evolve an entire new plasma membrane with a bilipid structure entirely different from what it’s genetically programed to synthesize and utilize. Dr. DeGrado’s molecules are designed to spontaneously latch on to both the hydrophillic outer layer of the membrane and bore into the hydrophobic interior fatty layer. When this happens, the membrane loses integrity and rips apart. The stuff in the cell is free then to diffuse out. The bacterium is then functionally dead.

To keep any of that from happening, the bacterium must present a different membrane without its peculiar hydrophyllic and hydrophobic layers—which are unique in bacteria compared to unaffected animal (human) cell membranes.

I’ve said it before. There simply cannot be any appearance of bacterial resistance to the PMX molecules.

PolyMedix molecules have no need to get through the plasma membrane of the bacteria. They must merely touch them, and they dissolve, so to speak. 


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PolyMedix molecules work—kill bacteria—in ways no existing antibiotic does. Moreover, and crucially, there is no foreseeable means by which any bacterium could evolve resistance. Notice that the PolyMedix lawyers have caused all the information from the company on this point to claim, so to speak, “Resistance is thought to be unlikely...,” or words to that effect. Those of us who know a bit about bacterial genetics and the structure and function of bacterial plasma membranes, know fully that nothing can stop the PolyMedix molecules, regardless.

The seminal phrase (and mechanism) for PMX efficacy is “membrane disruption.” No other antibiotic works this way. Penicillin, and all the rest, have to get themselves inserted inside the bacterium, where they bind on to, or otherwise disrupt crucial molecules, often essential enzymes. The PMX stuff all works from the outside, so no problems getting in.

And this is an important point, too. You mentioned that it took thousands of years for conventional resistance to occur. That’s probably not the case. Most antibiotics originated from naturally occurring molecules, often in soil. They have been confronting bacteria for millennia, and the bacteria already have genes, if expressed, that can fight them off—which they are now doing in MRSA and other resistant bacteria.

Innate, unexpressed resistance to PMX molecules will not exist. PolyMedix molecules are unique. They have on their surfaces a bunch of molecular “sticky points” and adjacent “repellant points” that when bumped against a bacterium, while merely floating around in blood, cause the bacterium’s plasma membrane to spontaneously break apart, the so-called “membrane disruption.” The PMX molecules are little armor-piercing devices that repeatedly poke holes in the bacteria, because of the unique chemistry of bacteria plasma membranes. The bacteria have no way to repair such rapid, almost instantaneous damage, nor do they have any way of making a functioning plasma membrane that does not have the “sticky spots.” It’s no-win for the germs. Period.

PMX 60056 by Falconer66a

Once PMX 60056 gets FDA approval, the entire surgical bleeding phenomenon changes. Yes, PMX 60056 just utterly stops or reverses the anti-clotting effects of heparin, without side effects—something that surgeons want to do just as soon as they end sew-up after a surgery.
But the much bigger thing is this. Heparin works wonderfully in stopping surgically-induced or surgically-coincidental blood clots. But the problem with heparin is that its anticoagulant properties continue unabated for a long time after surgery, allowing unwanted post-surgical bleeding. During surgery, physicians don’t want blood to be clotting anywhere in the body. At the surgical site, such bleeding can be stopped by cauterization or the tying off of larger blood vessels. No problem there. The surgeons can deal with surgical field bleeding. But after a surgery where heparin has been used, to keep clots from forming in other parts of the body, the risk of post-surgical bleeding can be significant (depending on the surgery). Consequently, heparin, right now, has limited usage, primarily because the present agent of reversing its anticoagulent properties, protamine, has a bunch of unwanted side effects.

Therefore, heparin, as good as it is, is used only when absolutely required, with well-known risks. When PMX 60056 becomes available, the entire surgical anticoagulant game is very likely to change, as the risks diminish markedly. With a syringe of 60056 in a surgical technician’s hands awaiting sew-up, the surgeon can rather freely administer heparin at the start. With PMX 60056, heparin is likely to be used much more commonly, perhaps by an order of magnitude.

Consequently, no one knows with any exactitude how big the PMX 60056 market will be. But surely it will larger than that of current heparin usage. As with other PolyMedix products, the medical game changes with PMX 60056.
 

Polymedix -vs- Tetraphase

Post from Falconer66a:

They (Tetraphase's compounds) are tetracycline-based. Their difference is that the company is able to synthesize new forms of tetracycline antibiotics that do not appear in nature.

That’s all well and good. There would be a very good chance that the company can come up with novel tetracyclines that would prove more effective than the older, existing ones.

But in comparison to PolyMedix’s antimicrobials, there’s one gigantic difference. Any tetracycline antibiotic, whether extracted from soil bacteria and purified (as with the original tetracycline), or if an existing tetracycline is chemically modified, or in the case of the novel, entirely synthesized tetracyclines of this company, they all have to get themselves inside the target bacterium, and must remain in there to work their bacterially lethal magic. That’s the problem. Sooner or later, pathogenic bacteria will evolve mechanisms to either keep out the new antibiotic, or will hike the active rejection and expelling of the molecules once they get inside the cell. Either way, the bacterial cells and their pathogenicity survive.

Not so, though, with PolyMedix molecules. They need merely bump up against the target bacterium and its plasma membrane is almost instantly disrupted. The cell’s chemical guts spill out, and the pathogenic game is over.