New Medication Against Heart Attack


by iansmith
Tags: attack, heart, medication
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#1
Dec9-03, 05:38 PM
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Town without heart attacks
Italian resort's genetic anomaly leads to a drug that could reverse coronary disease
_
Brad Evenson
National Post

December 9, 2003

The tiny Italian resort town of Limone sul Garda sits tucked along the western shore of Lake Garda, its scenic streets lined with oleander, olive and lemon trees. For centuries, it was best known for its mild Mediterranean climate and its delicious cold-pressed olive oil. But since 1980, the town's most famous export has been blood.

If studies confirm the astonishing potential of a protein called ApoA1 Milano found in the bloodstreams of 40 of Limone sul Garda's residents, millions of people could someday be cured of heart disease.

"It's very exciting," says Jean-Claude Tardif, director of clinical research at the Montreal Heart Institute. "It's really potentially a revolution in the treatment of coronary heart disease."

Last month, researchers from the Cleveland Clinic in Ohio reported infusions of the Italian protein reversed decades of cholesterol buildup in the arteries of heart patients in just a few weeks. Experts predict it will become a blockbuster drug worth billions of dollars.
http://www.canada.com/national/natio...e-ec318750ab9f
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Monique
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Dec9-03, 11:51 PM
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Garda.. good place to be.. little touristic, but alla.

But the ApoA1 I don't understand, they just found out that it works? It would have been my first guess since it is a major part of the lipoprotein aggregates. Out the top of my head it probably allows HDL to take up more cholesterol and bring it to the liver to be excreted (remember, we are unable to metabolize cholesterol, the only way out is excretion).
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Dec10-03, 07:27 AM
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The manufacturers of angioplasty balloons and stents are peeing in their pants!

zoobyshoe
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Dec10-03, 12:01 PM
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New Medication Against Heart Attack


I'm not getting how they are making use of this. Are they taking blood from these villagers, separating this stuff out, and injecting it into other people?
Monique
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Dec10-03, 12:04 PM
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Originally posted by zoobyshoe
I'm not getting how they are making use of this. Are they taking blood from these villagers, separating this stuff out, and injecting it into other people?
That would be waaaay to expensive, they have probably made some bacterial system into which they transfected (or would it be transformed?) the gene encoding for the protein with a strong promotor in front of it so that the expression is high, after which they can purify it.
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Dec10-03, 12:09 PM
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Originally posted by Monique
That would be waaaay to expensive, they have probably made some bacterial system into which they transfected (or would it be transformed?) the gene encoding for the protein with a strong promotor in front of it so that the expression is high, after which they can purify it.
This is the way proteins are usually replicated?
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Dec10-03, 12:22 PM
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Originally posted by zoobyshoe
This is the way proteins are usually replicated?
Yes. Insulin is produce by a genetically engineered E. coli. Some other protein are produce by yeast. the system are inexpensive and efficients.
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Dec10-03, 12:28 PM
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Originally posted by iansmith
Yes. Insulin is produce by a genetically engineered E. coli. Some other protein are produce by yeast. the system are inexpensive and efficients.
So, there is nothing you can think of that might make this medication particularly expensive to produce?

I'm just speculating as to whether the drug companies will find a rationalization to jack up the price unfairly because it is sure to be such a widely desired treatment.

-zoob
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Dec10-03, 12:28 PM
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The only problem with the system is that the bacteria (also yeast?) will eventually loose the foreign piece of DNA.

This due to the stress that is generated by having to over-produce this specific protein that has no function for the micro-organism.

A cell that has lost the piece of DNA will have a significant growth advantage and will eventually take over the culture.

Also, impurities left after purification would be able to generate an immune response, I imagine.

But overall it is a really clever way to produce this kind of medication. Not just bacteria are used, also rabbits and maybe cows. The protein is specifically expressed in the mamary glands and will be excreted in the milk after which it can be purified. I guess they use these higher eukaryotes, since some proteins need post-translational modifications which don't take place in bacteria.
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Dec10-03, 12:35 PM
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Originally posted by zoobyshoe
So, there is nothing you can think of that might make this medication particularly expensive to produce?

I'm just speculating as to whether the drug companies will find a rationalization to jack up the price unfairly because it is sure to be such a widely desired treatment.

-zoob
I don't think maintaining high grades cultures is cheap, but it is cheaper than isolating it from blood and the quantities that are produced allow mass scale distribution.

HAH! Drug companies jacking up prices.. do you know how much profit they can make? Let me give you an example: Genzyme, a Massachusets based company, started out with like 15 people or so. They took over a project from academic researchers, the whole idea of making the medicine was already there, little research was required but setting up a system to produce and quality proof the production.

Now, the researchers who did all the work get nill % off the profit into which all those years of effort and work was put into. The company hitched a ride and has now grown to ~5000 people.

So, you might wonder, how much is their profit? Let me tell you: 95%. Yes, 5% of the cost is what they actually have to spend for the production. The 95% is what goes into their pocket. Surprised? :)
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Dec10-03, 12:37 PM
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Originally posted by zoobyshoe
So, there is nothing you can think of that might make this medication particularly expensive to produce?

I'm just speculating as to whether the drug companies will find a rationalization to jack up the price unfairly because it is sure to be such a widely desired treatment.
There is the R & D involve for the pricing and this is the expensive part of the product according to their rational. But it is less expensive because it can be mass produce more efficeintly than if you have to isolate the protein from its source.

Insuline is to be insolated from pig pancreas. It was expnsive and the product was not readily available.

Originally posted by Monique
But overall it is a really clever way to produce this kind of medication. Not just bacteria are used, also rabbits and maybe cows. The protein is specifically expressed in the mamary glands and will be excreted in the milk after which it can be purified. I guess they use these higher eukaryotes, since some proteins need post-translational modifications which don't take place in bacteria.
This compagny can isolate spider web from goat milk

Nexia Biotechnologies
http://nexiabiotech.com/en/01_tech/08.php

They also trying to use plants instead of animals. Cheaper, easier to produce, not as energy demanding and less ethic problem.
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Dec10-03, 12:37 PM
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Btw, the patent has already expired for this medication, but generic versions have not be made since the compition would be too great with the already well established firm.
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Dec10-03, 12:55 PM
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Researchers actually once did a trial in which they injected people with HDL (the good cholesterol).

The problem with using this molecule is that it is an aggregate of lipoproteins and cholesterol and other proteins such as the apolipoproteins (Apo) and thus very hard to produce. It never took off the ground because of this and other routes have been chosen.
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Dec10-03, 01:37 PM
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Originally posted by Monique
So, you might wonder, how much is their profit? Let me tell you: 95%. Yes, 5% of the cost is what they actually have to spend for the production. The 95% is what goes into their pocket. Surprised? :)
This kind of profit margin is just about unbelievable to me. I suppose the phenomenon of medical insurance is what makes it possible. Not that I understand the workings of that.
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Dec10-03, 01:44 PM
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Originally posted by iansmith
This compagny can isolate spider web from goat milk
Et, bien? Pourquoi?

What does anyone want with spider webs? Why would goats be a better source than spiders?
Monique
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Dec10-03, 02:14 PM
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Originally posted by zoobyshoe
This kind of profit margin is just about unbelievable to me. I suppose the phenomenon of medical insurance is what makes it possible. Not that I understand the workings of that.
Normally it would not be that outragious, figuring the years (decade in some cases) of R&D that has gone into the research.

They have to earn that back somehow, that is why brand medicines are so expensive: they want to make optimal use of the years that their patent allows them to be the sole producer and thus have no competititors.

In this case I think it is outragious, since the company has not spend all the years doing R&D, the academia has. And also it is the sole producer, even though the patent has expired. The thinking of the company: with this medicine we are now earning the resources to research other venues of disease.

In my opinion the company should set up a system, in which patients of the poorer countries where the insurance system is not able to cough up $300,000 per patient per year (and this continues life-long), are benifited with donations of some sort.

Right now the group of academic researchers who first came up with the data have set up a European Working Group which helps such patients. Since the irony is: with this life-long treatment a patient can lead an almost normal life, otherwise it will get serious physical abnormalities (a spleen weighing 13 kg for instance).

Maybe the company has something like this in place, I am not sure, I think they should :)
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Dec10-03, 02:15 PM
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Originally posted by zoobyshoe
What does anyone want with spider webs? Why would goats be a better source than spiders?
Spider Web is one of the more resitant fiber that human knows. It could be use for fireproofing materials, bullet proofing or any other material that need reinforcement.

People do collect the wed from spider but it is a long and intensive manual labor. One indidual spider does not give as much web as one goat. For the goat all you have to do is to acquire the milk and isolate the protein. They are still working on the efficienty of the method.
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Dec10-03, 02:17 PM
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Originally posted by zoobyshoe
Et, bien? Pourquoi?

What does anyone want with spider webs? Why would goats be a better source than spiders?
Spiderweb fiber is one of the strongest compounds known to exist in nature. What you can do with that? Just imagine :)

Why goats are a better source.. well.. [:D] how much web does a spider make in a day and how much milk does a goat make a day.. quantities ar the issue here.


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