dan,
thank you for the response, from a scientific standpoint could you explain why the average/lean monkey didnt show any weight loss? i mean if this peptide works by actually destroying fat cells (rather than simply shrinking them) then i do not understand the results. i also heard that the majority of the fat loss induced by adipotide was visceral fat rather than subcutaneous fat. "MRI and DEXA imaging confirmed that weight loss in the rhesus monkeys occurred primarily because of visceral fat loss." from source (high-fat-nutrition.blogspot.com/2011/11/adipotide-and-bad-fat.html). and from what i understand fat cell numbers can never be reduced in adult life, and that appetite is directly linked to the number of fat cells one has. this makes sense as to why as an overweight person losing fat AND MAINTAINING that loss is a constant battle against elevated ghrelin levels, so on all fronts this drug has the potential to be the "one" we have been waiting for. and lastly i would love to try it but as you mentioned this isnt a drug to try if your on a budget, and i dont think $6000 is doable for me, so do you think as demand steadily increases the prices will drop?
Hi Zomorodi:
Adipotide does not kill fat cells directly. It does not recognize fat cells, or lipids or fatty acids. What it recognizes and kills are the epithelial cells that line the capillaries that feed the fat cells with blood and oxygen. These epithelial cells have a protein on their surface, Prohibitin, that other cells in the body do not have and Prohibitin binds to the peptide sequence KGGRAKD. This means that if you make a peptide with the sequence KGGRAKD at one end, it will home to capillaries of adipose tissue and nowhere else. Then you simply attach a death signal to the other end of the peptide and you have the ultimate weapon to kill fat tissue by cutting off its oxygen supply. Its absolutely brilliant and the inventors (Arap and Pasqualini) deserve to make a fortune on this.
The reason that lean animals are unaffected by adipotide is because they have very little adipose tissue, and hence very little of the epithelial cells that line the capillaries that feed adipose tissue. Since the target of adipotide is the Prohibitin protein that is only found on the capillaries in adipose tissue, and since lean animals do not have such capillaries, adipotide has no target and no effect. Lean animals still have some fat cells elsewhere in the body and they still have lipids and fatty acids in every cell in the body, but these molecules are not the target of adipotide. Therefore adipotide circulates harmlessly in the blood of lean animals and is excreted through the kidneys into the urine.
But the targeting and killing is not the whole story. Arap and Pasqualini also figured out how to make the peptide biostable so that only modest doses are needed to see the desired effect. The problem is that the body is laced with enzymes (proteases) that degrade peptides. This is a normal and necessary function, as the body makes proteins and peptides and must also degrade them. In order to make adipotide resistant to proteases, they did 2 things. They made the death signal with D amino acids that are unnatural and cannot be recognized by proteases. Fortunately the death signal still works when the sequence KLAKLAK is in the D form. For the homing sequence KGGRAKD, they add cysteines amino acids on each end to obtain the sequence you see in their paper: CKGGRAKDC. These 2 cysteines each have one free sulfur atom and when the peptide solution is diluted and the pH is lowered, the 2 sulfur atoms in the same molecule will bond to each other, cyclizing the peptide. Since the zipcode part of the peptide now has no free end, the proteases cannot chew it up. Absolutely brilliant. Keep in mind that peptide cyclization is used for may peptide drugs, and Arap/Pasqualini were using a trick that others had developed. The death signal was also known. Their big contribution was to find the zipcode homing sequence for the capillaries in fat tissue (KGGRAKD) and then to put the pieces together to create the most elegant solution to the obesity problem that one could possibly imagine.
""Dear Sir. I want to buy for research purposes, 1 gram of Prohibitin-Targeting Peptide 1. Can I ask you the cost and conditions?
Here is yesterday's response from Great White Peptides:
We do not carry this anymore
That sucks. That really sucks. """
It doesn't suck. Not only was GWP charging way too much ($15,000 per gram) but they were breaking the law by selling adipotide because there is a patent on it. Apparently GWP got a letter in the past 2 weeks from the lawyers at Arrowhead Research (which has licensed the patents) and/or the University of Texas that owns the patents and that convinced them that they will be sued big time if they don't stop selling this peptide. So don't expect to see adipotide for sale in the USA, Canada, or the EU before Arrowhead and its partners start selling FDA approved adipotide in 10 years or so. The good news is that the University of Texas only filed patents in the US, Canada, and the EU for the basic idea of making a peptide with the sequence CKGGRAKDC-GG-(D)-KLAKLAKKLAKLAK , cyclizing it, and injecting it to obtain weight loss. This means that you can make, sell, buy and use this peptide anywhere in the world outside of the US, Canada, and the EU without infringing on these patents.
Perhaps the medical authorites in Mexico, Morocco, and other such places will not be as slow as the FDA in approving CKGGRAKDC-GG-(D)-KLAKLAKKLAKLAK (we should probably not call it adipotide because this name is a trademark now) and it will probably be available in these countries sooner and at a reasonable price. The cost per gram of this peptide when made in kilogram batches will be less than $1000. I can see weight loss clinics in Mexico offering this peptide to patients under a doctor's guidance in less than 5 years. Mexico also has a big problem with obesity, which drains billions of dollars from their economy from higher medical costs, lost productivity, etc. The FDA might think they need 10 years but I am sure the authorities in at least one country not covered by the patents will not be so timid (India, China, Israel, Somalia, Bolivia, North Korea?).
In the EU, 20 countries are listed as designated states on the EU patent, including all the big ones. San Marino, Malta, Norway, Andorra, Iceland, Hungary, Czech Republic, and a number of others, however, are not listed. Norway is one of the richest countries in the world due to their oil resources, so they have the money, the educated populace, and the freedom to operate (ie no worries over the adipotide patents) and a fair number of body builders to try it out. Any Norwegians out there that want to give it a try?
Dan
