Mutation found that cures heart disease

djf, with references

[djf]

In 1980, a man from a small town called Limone Sul Garda in northern Italy went to a doctor for some problem, not heart related.



Testing of his blood showed very high levels of triglycerides, and very low levels of HDL, the good form of cholesterol. By all rights, the man should have either been dead from, or in imminent danger of a heart attack.

But his arteries were clear.
Analysis of his blood showed he had a very special form of Lipoprotein, a type of HDL. And further work with this particular type of Lipoprotein revealed astounding results.

In some of the initial small scale tests of this form of HDL, volunteers were given one shot a week of it, for a trial that lasted five weeks.

Measurements of the blockage in their arteries showed that total blockage was reduced by 4% in five weeks. While this may not sound like much, to a cardiologist, it's equivalent to taking years off of your cardiac age.

Further testing and analysis with animals show fantastic results. While standard HDL's are desirable, this substance has been shown to for all intents and purposes, to completely reverse heart disease.

Various articles have referred to it as "Drano for the arteries".

Research is continuing with a slightly modified, bioengineered form and results are extremely promising.

The cholesterol (and yes, it is cholesterol) that is saving these people's lives is called ApoA-Milano.

And of the forty or fifty people in that tiny Italian town, all descended from a man born in 1760, a man who had a small change in his genes, not a single one has yet to die from heart disease!


http://www.lbl.gov/Science-Articles/Archive/LSD-Milano-Bielicki.html
http://www.usatoday.com/news/health/2006-01-08-heart-disease-cover_x.htm
http://jama.ama-assn.org/cgi/content/abstract/290/17/2292

There are 96 references on PubMed for apoa milano

[buffyt]

Interesting, too:

The delta 32 mutation, however, effectively blocks the crucial gateway into human cells the virus needs. In the case of Steve Crohn, whose partner was the fifth person to die from AIDS, possessing the CCR5 mutation has prevented him from contracting the virus.

http://www.pbs.org/wnet/secrets/case_plague/index.html

No one knows exactly why, but in the late 1320s or early 1330s, bubonic plague broke out in China's Gobi desert. Spread by flea-infested rats, it didn't take long for the disease to reach Europe. In October of 1347, a Genoese ship fleet returning from the Black Sea -- a key trade link with China -- landed in Messina, Sicily. Most of those on board were already dead, and the ships were ordered out of harbor. But it was too late. The town was soon overcome with pestilence, and from there, the disease quickly spread north along trade routes -- through Italy and across the European continent. By the following spring, it had reached as far north as England, and within five years, it had killed 25 million people -- one-third of the European population.

The bubonic plague is caused by a bacterium called Yersinia pestis and is characterized by chills, fever, vomiting, diarrhea, and the formation of black boils in the armpits, neck, and groin. Though the disease was originally called the "Great Mortality" and the "Great Pestilence," the name "Black Death" was eventually adopted because of these black boils, which derive their color from dried blood under the skin caused by internal bleeding. In certain cases the bacterium spreads to the victims' lungs, causing them to fill with frothy, bloody liquid. This derivation of the disease is called pneumonic plague, and can quickly spread from person to person through the air. It is almost always lethal.

The plague first spread to Britain in 1348, travelling from Bristol to Oxford and London in several days. In 1665, perhaps the worst of the English epidemics broke out in London. That summer, the nobility and clergy fled the city, as some 7,000 people died each week. As many as 100,000 lives were lost before winter killed the fleas and the epidemic tapered off. Contemporary medicine could provide no explanation for the sickness, and most doctors were afraid to offer treatment. In an attempt to keep from being infected, the few physicians who did risk exposure wore leather masks with glass eyes and a long beak filled with herbs and spices that were thought to ward off the illness. Even one person in a household showing plague-like symptoms was enough to mandate a 40-day quarantine for the whole home -- a virtual death sentence for everyone living in it.

In September 1665, George Viccars, a tailor in the small, central-England village of Eyam, received a parcel of cloth ridden with plague-infected fleas from London. Four days later, Viccars died. By the end of the month, five more villagers had succumbed to the plague. The panicked town turned to their rector, William Mompesson, who persuaded them to quarantine the entire village to prevent the bacterium from spreading throughout the region. It seemed like suicide. A year later, the first outsiders ventured into Eyam, expecting a ghost town. Yet, miraculously, half the town had survived. How did so many villagers live through the most devastating disease known to man?

Local Eyam lore tells befuddling stories of plague survivors who had close contact with the bacterium but never caught the disease. Elizabeth Hancock buried six children and her husband in a week, but never became ill. The village gravedigger handled hundreds of plague-ravaged corpses, but survived as well. Could these people have somehow been immune to the Black Death?

Dr. Stephen O'Brien of the National Institutes of Health in Washington D.C. suggests they were. His work with HIV and the mutated form of the gene CCR5, called "delta 32," led him to Eyam. In 1996, research showed that delta 32 prevents HIV from entering human cells and infecting the body. O'Brien thought this principle could be applied to the plague bacteria, which affects the body in a similar manner. To determine whether the Eyam plague survivors may have carried delta 32, O'Brien tested the DNA of their modern-day descendents. What he found out was startling ...

You may possess a genetic mutation. Most people would probably be aghast to learn that one of their genes is malformed. But before you start asking, "What does that mean? Will it make me sick someday? Will I pass it on to my children?" bear in mind that a mutation of the CCR5 gene -- called "delta 32" in its mutated form -- has no adverse effect on humans. In fact, possessing delta 32 could save your life, and the lives of your children.

"It's highly unusual," says Dr. Stephen J. O'Brien of the National Institutes of Health in Washington D.C. "Most genes, if you knock them out, cause serious diseases like cystic fibrosis or sickle cell anemia or diabetes. But CCR5-delta32 is rather innocuous to its carriers. The reason seems to be that the normal function of CCR5 is redundant in our genes; that several other genes can perform the same function."

"The non-mutated form is what's called a chemokine receptor," he says. Chemokines are protein distress calls released by an injured region of your body. "The normal function of the CCR5 gene is to act as a retriever of the chemokine distress signal from these bruises, which will then be alleviated by the chemokines."

This may not sound exciting, but delta 32 is a powerful mistake. HIV, the virus that causes AIDS, attacks the human immune system, infecting the white blood cells sent to destroy it. The delta 32 mutation, however, effectively blocks the crucial gateway into human cells the virus needs. In the case of Steve Crohn, whose partner was the fifth person to die from AIDS, possessing the CCR5 mutation has prevented him from contracting the virus.

O'Brien explains further, "In order to have total resistance to HIV, you have to carry two doses of the mutated gene -- one from each parent. If you get only one dose, you will not be resistant to infection. However, you may be able to delay the onset of HIV once you become infected. That's because, in patients with one copy of the mutation, the amount of 'portals' or 'doorways' that HIV can use is reduced by about 50 percent. That slows down virus replication, which is the most important factor in AIDS progression."

O'Brien's work on AIDS led him to another disease that delta 32 could prevent, the plague. "They both, upon entering the body, infect the microphages, which are the first line of defense against bacterial infections," he says. "Over the course of evolution, many bugs and pathogens have become extinct because the body learned how to defend itself against them. So the ones that are around today, like HIV and the plague, are pretty savvy -- HIV, for example, specifically attacks and kills the very cells that are designed to kill it. Both these pathogens have developed very clever ways around our immunological defenses."

The results of the Eyam study suggest that delta 32 may have helped save Europe from the bubonic plague pandemic. It seems logical, then, that this could be confirmed by an experiment in which the plague bacterium is injected into the cells of someone possessing the delta 32 mutation. "We have attempted to design experiments that allow us to expose the plague to the lymphocytes of different people, including Steve Crohn," O'Brien says. "But so far we haven't been able to design that kind of experiment ... to do that experiment, you would need to isolate that particular kind of cell. You would need to isolate the exact strain of the plague, and you would need to expose them together."

Nevertheless, delta 32 seems to be a formidable defense the human body has developed in response to ages of pathogenic exposure. And though we may just be getting acquainted with it, delta 32 has been protecting humans for ages. O'Brien suspects the mutation has been around since long before the Black Death. "There have been human remains dug up from graves in Scandinavia -- bodies 3,000 and 4,000 years old -- in which they actually found the mutation, through DNA typing. So there are all kinds of pieces in this puzzle that are coming together."

[Itzlzha]

Scientific arrogance is commonplace. Physicians consider themselves to be experts in their own field. If a majority of physicians do not endorse a new therapy, they collectively rely on public recognition of their own "expertise" to discount a new concept that they themselves have not yet embraced.

OH, have you touched on my HUGE issue now!

I am currently crippled due to an OTJ accident (My rt knee hyperextended backwards, and the kneecap dislocated axially!). I have had 1 surgery, and there is a massive complication...but other than the original surgeon...every frickin' Orthopaedist has called it Chondromalacia with the kneecap...it AIN'T THE FRICKIN' KNEECAP! It's medial INSIDE the actual feomoral joint!

They are all NO better than the Leeches of the 8th Century! They plug the lastest drug (because they get lovely goodies for doing so, and don't think the law changes have stopped THAT process!), and they all go for the easiest answer, rather than LISTENING to an itelligent patient who has CONSISTENTLY described the SAME FRICKIN' pain and issues since the accident!

The Medical Profession is stocked by the very same OVEREDJUMIKATED IDIOTS that plague Society in General.

If these clowns took their Porsche to a mechanic who simply changed the oil every time, no matter HOW much noise the engine made...would THEY tolerate it?

YEESH!

[Mad Dawg]

What are you saying? That I should smile and grin when someone suggests that the "genepool is getting polluted"? Doesn't that imply that the "genepool needs to be cleaned up"?

No, as a matter of fact and logic it does NOT imply that. That is only one of several responses to the problem and it is not a necessary response. It's not an implication in the strict sense eof the word.

[Appalled but Not Surprised]

It's not "Lady of Spain" that's the tune in the air, but the Horst Wessel Leid. And I ain't the one singing it....

Referring to some humans as having "genetically weaker" structures than others is the first step of a one way ticket to Auschwitz. Who do you think you are? God?

[Uriah_lost]

If your "survival of the fittest" line of thinking were to prevail my children would all be dead now from childhood illnesses. At what point do you draw the line. When do we say "sorry you have to die for the good of the gene pool" and who gets to say it? Did you get sick as a child? Did you have your appendix out? When would you have died and who would have told your parents "too bad, he's inferior"?Sorry, you and I can make those kind of decisions for ourselves but not for others.

[djf]

Excellent summary. TY!

[jennyp]

they need this for cancer as well

They have, at least in mice. This article is from 3 years ago, but I haven't heard anything else about this discovery since:

A cancer-proof mouse, which can survive being injected with any number of cancer cells, has been discovered by US scientists. The discovery of the resistant mouse could pave the way for future gene or drug therapies if the mechanism by which it fights cancer can be understood

Researchers at the Wake Forest University School of Medicine in North Carolina have now bred a colony of 700 cancer-proof mice from the resistant male they stumbled across while doing other experiments.

Doctors have known for many years that in rare cases, cancers can mysteriously clear up of their own accord. But this is the first time such cancer-killing ability has been shown to be genetic.

"The power of this resistance seems to be unlimited," said biochemist Zheng Cui, the study leader. "You can give them many, many tumour cells and the mice get rid of them."

"This is at a preliminary stage, but very promising," adds pathologist Mark Willingham, another member of the team. "Our hope is that, some day, this will have an impact on human cancer." ...

[Dustbunny]

I heard of this before. Will have to search it out on Google later.

[jennyp]

I remember reading up on this some years ago. At the time they were trying to isolate the protein so they could figure out how to produce it in quantity. I hadn't heard any updates and assumed it had been a dry hole. I'm hoping that this is a sign that this may still be a viable treatment option some time in the future(sooner better than later) Thanks for putting this up.

BTW, when I first read about this, I realized that the company that was developing it, Esperion Therapeutics, would get bought out at a nice price. So I resolved to keep watching the stock for a good place to buy some, after the initial run-up on the news died down.

And then I forgot all about it. Then I read that Pfizer bought them up for $1.3 billion, a 50% premium over their stock price. AAARRGGHH!!! You snooze you lose. >:-(

[Stellar Dendrite]

awesome, thank you so much :)

[Uriah_lost]

I'm expecting they will patent the method of production (likely several) since it's likely that they would have a hard time getting a patent on the substance. I thought about the stock play at the time too and also lost track.
Woulda, coulda, shoulda, eh?

[aruanan]

And in fact you NEED cholesterol, because sitting in the sun converts some of your cholesterol to chole-calciferol, otherwise known as vitamin D3. And the recent findings with vitamin D and cancer are almost as stunning as this one. I think cholesterol plays a role in collagen synthesis too.

It's important for cell membranes and critical for the myelin sheaths of nerve cells. Some hard core vegetarians have severely screwed up their children's neurological development by a lack of dietary cholesterol.

As far as good cholesterol versus bad cholesterol, the difference in the particles isn't in the cholesterol component because the HDL is transporting the same cholesterol that is in LDL. It's just removing it from the LDL:

Contrary to popular understanding, when we speak of "good and bad" blood cholesterol levels, we are not speaking of different types of cholesterol molecules. Due to their poor solubility in the blood stream, cholesterol, triglycerides and other lipids require transport vehicles such as lipoprotein particles. It is these transport vehicles that determine the "good and bad" nature of cholesterol.