November 04, 2003
Synthetic HDL Cholesterol Reduces Artery Clogging In 6 Weeks

The reduction of clogging was 4% in just 6 weeks.

Intravenous doses of a synthetic component of "good" cholesterol reduced artery disease in just six weeks in a small study with startlingly big implications for treating the nation's No. 1 killer.

How would you like to quickly reduce your risk of heart attacks or the pain from angina?

In a small, preliminary study, the laboratory-made substance, which mimics a type of cholesterol discovered in a group of surprisingly healthy villagers in rural Italy, significantly reduced in just six weeks the amount of plaque narrowing arteries of heart attack and chest pain patients, the researchers reported.

Note to life extension skeptics: With this report is there any reason to think artery hardening will be a major cause of mortality in industrialized countries 20 years from now?

The drug is made using recombinant DNA that matches the gene sequence for HDL cholesterol found in a small population of people in northern Italy. (same article here)

The development of this investigational drug is an unusual story. About 30 years ago, researchers discovered 40 individuals in Limone Sul Garda in Northern Italy who appeared perfectly healthy, despite having very low levels of good cholesterol. Ordinarily, such people would have a high risk of heart disease, but these people did not. Intrigued, researchers wanted to find out why. Their studies revealed a variant in a protein known as Apolipoprotein A- I, which is a component of HDL. This variant was named ApoA-I Milano after the city of Milan, where the initial laboratory work was done.

ApoA-I Milano is being developed into a potential treatment for heart disease by Esperion Therapeutics Inc., an Ann Arbor, Mich.-based biopharmaceutical company. Esperion's investigational treatment, designated ETC-216, is a recombinant version of ApoA-I Milano combined with a phospholipid. After pre-clinical studies showed rapid removal of plaques from diseased arteries, scientists at Esperion came to Dr. Nissen to help them design a study to determine whether infusions of the ApoA-I Milano/phospholipid complex could reverse coronary plaque buildup in patients with heart disease.

The Cleveland Clinic-directed study administered the ApoA-I Milano/phospholipid complex intravenously over a five-week period to a randomized group of patients initially hospitalized for acute chest pain. Researchers measured arterial plaques using intravascular ultrasound (IVUS) before and after the six-week study. Patients who were given the synthetic protein showed a dramatic decrease in arterial plaques, whereas a comparison group given saline showed no change in plaques.

It sounds like it is time for phase 3 clinical trials.

"These results demonstrate for the first time that it is possible to rapidly regress the major underlying cause of heart attack," said Roger S. Newton, Ph.D., President and CEO of Esperion Therapeutics. "By enhancing the removal of cholesterol from plaques in artery walls, a process known as reverse lipid transport, HDL therapy may provide an innovative approach to the treatment of atherosclerosis. We are excited about these results and look forward to continuing the development of ETC-216 in more patients with longer follow-up and assessing more endpoints, including morbidity and mortality."

In the Phase 2 clinical trial, 47 patients with acute coronary syndromes (ACS) received five weekly intravenous infusions of placebo (n=11 patients), ETC-216 at 15 mg/kg (n=21 patients) and ETC-216 at 45 mg/kg (n=15 patients). Plaque volume was measured before treatment and within two weeks after the final infusion using intravascular ultrasound (IVUS). With IVUS, a tiny ultrasound probe is inserted into the coronary artery to directly image and measure the size of the atherosclerotic plaques. The study revealed a statistically significant reduction (p=0.02) in percent atheroma (plaque) volume in the combined ETC-216 treatment groups comparing end-of-treatment values to baseline values.

Additional IVUS endpoints in the trial, such as total atheroma volume and maximum atheroma thickness, also showed statistically significant improvements.

"This study shows that ETC-216 could become an important new option for the treatment of people affected by atherosclerosis," said Steven E. Nissen, M.D., F.A.C.C., principal investigator of the study and medical director of the Cleveland Clinic Cardiovascular Coordinating Center. "We now have evidence that it is possible to rapidly and directly reverse the atherosclerotic disease process in artery walls."

Eventually in the much longer term (10 to 20 years is my guess) we can expect to see a gene therapy developed to deliver ApoA-I Milano protein gene into the liver of the vast bulk of us who do not have this beneficial variant of the gene (Update: the more likely scenario would be to just add more of the regular ApoA-I that would be expressed at a higher level to raise normal blood HDL levels). That way the benefit would be there all the time. To derive an even bigger benefit the gene therapy could also deliver a genetic variation Cholestryl Ester Transfer Protein (CETP) variant that makes cholesterol molecules bigger and extends life as a result.

Esperion's web site explains the mechanism of action.

The RLT pathway is a four-step process responsible for removing excess cholesterol and other lipids from the walls of arteries and other tissues, and transporting them to the liver for elimination from the body. The first step is the removal of cholesterol from the walls of arteries by HDL in a process called "cholesterol removal". In the second step, cholesterol is converted to a new form that is more tightly associated with HDL as it is carried in the blood; this process is called "cholesterol conversion". The third step is the transport and delivery of that converted cholesterol to the liver in a process called "cholesterol transport". The final step is the transformation and discarding of cholesterol by the liver in a process known as "cholesterol elimination". We believe our product candidates have the potential to enhance the effectiveness of these four steps in the RLT pathway in humans.

In a healthy human body, there is a balance between the delivery and removal of cholesterol. Over time, however, an imbalance can occur in our bodies in which there is too much cholesterol delivery by LDL and too little removal by HDL. When people have a high level of LDL-cholesterol, or LDL-C, and a low level of HDL-C, the imbalance results in more cholesterol being deposited in arterial walls than being removed. This imbalance can also be exaggerated by, among other factors, age, gender, high blood pressure, smoking, diabetes, obesity, genetic factors, physical inactivity and consumption of a high fat diet. The excess cholesterol carried in the blood in LDL particles can be deposited throughout the body, but can frequently end up in the arterial walls, especially those found in the heart. As a consequence, repeated deposits of cholesterol called plaque can form and possibly narrow the arteries, which may lead to acute chest pain (i.e. angina) or a heart attack. These are known as the "acute coronary syndromes".

As more genetic variants that affect health and longevity are found look for attempts to basically take "best of breed" genetic variations and stuff them all into each person who wants them. A lot of genes are expressed in only certain parts of the body and it may be practical to, for instance, upgrade livers to make better blood proteins. The eventual development of the ability to easily grow new replacement organs will facilitate this trend as people will get organs replaced with younger organs and in the process will opt to get genetic improvements added to the starter cells used to grow their new replacement organs.

Update: ApoA-I Milano was chosen because it is patented, not because it is any better than the more common form of apoA-I.

A second but obvious choice would be to simply give people H.D.L., infusing it into their veins. But there was a problem. The idea of giving ordinary H.D.L. was in the public domain and was not protected by patent, and so companies were not interested.

There was, however, one H.D.L. that had been patented, and Dr. Roger Newton, the president and chief executive of Esperion Therapeutics, a small company in Ann Arbor, licensed the rights to develop it.

Again, the main advantage of the Milano type of HDL is that it is patented.

Rader noted that there could be nothing particularly special about this particular form of HDL. It could be that it's the only one that's been tested this way because it's a form of HDL that can be patented. Other companies are developing different ways of using HDL to fight heart disease, such as drugs that boost the body's own production of HDL.

So this therapeutic approach works simply by raising the amount of apoA-I, which is a component of HDL cholesterol molecules.

This illustrates a real serious problem in the development of new treatments: if the infusion of naturally occurring compounds produced by the body is not going to be pursued all that vigorously because most of the compounds are not patentabe then the rate of advance of new and very useful therapies will be much slower. The fact that apoA-1Milano happened to have been patented (perhaps before US patent laws changed to make it harder to patent human genes?) turns out to be very beneficial to us all in this case because it provided an incentive for a company to pursue the various rather expensive phases of animal and human trials.

Perhaps what is needed is some regulatory category for drugs that functions as a proxy for a patent that provides sole ability to sell a compound for some period of time of a company takes the time to go thru regulatory approval steps.

Update II: The Cleveland Clinic has also done recent work on injecting into the heart cells that express stromal cell derived factor-1 (SDF-1) so that the SDF-1 will instruct stem cells to repair the heart.

Previous studies have indicated that damaged heart muscle could be regenerated by directly injecting stem cells into the bloodstream or by chemically mobilizing stem cells from bone marrow either prior to a heart attack or within 48 hours afterward. At The Cleveland Clinic, Dr. Penn and his colleagues looked at the potential of stem cells in repairing hearts weeks after a heart attack, during congestive heart failure. To determine whether SDF-1 was sufficient to induce stem cell homing and recovery of heart function, investigators transplanted cells that expressed SDF-1 into hearts eight weeks following a heart attack. Their research showed that re-establishing SDF-1 expression in the heart led to the homing of circulating stem cells to the injured organ, the growth of new blood cells and the recovery of cardiac tissue. Reintroducing SDF-1 to the heart yielded nearly a 90 percent increase in heart function compared to hearts treated with cells alone. Just increasing the number of circulating stem cells using drugs that induce stem-cell mobilization eight weeks after a heart attack was not enough to initiate meaningful tissue regeneration, supporting the notion that repair to the damaged tissue is possible for only a limited amount of time following the heart attack. Finally, this research suggests a clinically viable strategy for delivering this molecule that can be tested in future trials involving other organ systems.

Update III: Derek Lowe thinks it is possible to construct a patentable version of natural Apo-A1.

Note also that the natural, presumably unpatentable, form of Apo-A1 has been tweaked and modified quite a bit in its clinical studies. There are, I should think, eminently patentable processes there. Anyone, for example, who found a way to get around the purification difficulties of the native protein would patent the method immediately, and they'd get it, too. Any nonobvious formulations or dosing methods would be patentable - just find one that works. And I haven't even mentioned all the peptide analogs that people have been making - patentable, every one of 'em.

Update III: A September 26, 2004 report claims that the Catholic Medical Center in Manchester New Hampshire expects to be participating in the next round of Pfizer's ApoA-I Milano clinical trials which have been temporarily delayed for a reorganization.

Dr. Mary McGowan is director of the Cholesterol Management Center at CMC’s New England Heart Institute. She explained the company that developed the treatment— known as ApoA-I Milano — has since been purchased by the pharmaceutical giant Pfizer, and that has temporarily delayed the start of clinical trials while the company is reorganized.

McGowan said the NEHI has worked on cholesterol studies with Pfizer in the past. And she said last week, “I think there’s very little doubt that we’ll be working with ApoA-I Milano.”

Most clinical trial enrollments are done through the medical centers conducting the trials. So readers would be better off contacting the Cleveland Clinic or the Catholic Medical Center in hopes of getting in on the next round of trials.

Share |      Randall Parker, 2003 November 04 03:06 PM  Biotech Therapies

Bob Badour said at November 5, 2003 8:08 PM:

Perhaps what is needed is some regulatory category for drugs that functions as a proxy for a patent ...

Something along the lines of a land registry for uses of non-patentable compounds. Someone stakes a claim for a prospective use, and gets a patent-like monopoly to the prospective use in exchange for funding the trials. That worked for gold rushes. I cannot think of any objections to the idea. It sounds like a good idea to me.

anna said at November 6, 2003 1:02 PM:

better yet, universal health insurance. Then the govt would have an incentive to develop cheap medical treatments. I think it's coming.

Randall Parker said at November 6, 2003 1:35 PM:

Anna, The countries that have more taxpayer funded medical care all spend much less on medical research than does the United States. That is because the political demand for all biomedical money to go toward immediate treatments of those who are sick now is greater than the demand for funding longer term research projects to produce treatments for those who are not sick yet. Plus, all those countries put up obstacles for the adoption of new medical technologies and drugs. Canada is an excellent example where many drugs available in the United States are not available in Canada and reach market in Canada years later than they do in the US. Ditto for diagnostic machines.

So government a medical takeover would slow medical research, not accelerate it.

Bob Badour said at November 6, 2003 6:47 PM:

To amplify Randall's comments, I live in Canada. It took me 5 years to get a family doctor, which meant I was effectively shut out of "universal" single-tier medicine in Canada. After finally getting a family doctor, I had to wait ten months for an appointment with a specialist for a simple lower GI scope.

Anna, be very careful what you wish for because you might just get it.

Anthony Fasulo said at November 7, 2003 7:51 AM:


How may I obtain this drug? I have a situation in which my cardiologist
says that he cannot approach blockage I have in the rear of my heart. I am
willing to partake of any experiment and comply with all guidelines necessary
for my being ble to treat my heart disease.

Thank You,

Anthony Fasulo

Maureen Murray said at November 7, 2003 8:19 AM:

How can I find out where new clinical trials for the synthetic HDL will be held and how can I sign up to participate? Thank you.

Randall Parker said at November 7, 2003 9:04 AM:

People who want to be in a future clinical trial might want to contact either the Cleveland Clinic or Esperion Therapeutics. Try clicking thru to their web sites and looking for contact numbers. My guess is that a stage III trial won't start for some months since they will need to review with the FDA what they've found so far. But if you are desperate best to try to see if they are taking names yet.

Patrick Cee said at November 7, 2003 10:44 AM:

Why not develop a more substantial public health system that functions in parallel with the private medical establishment? Then wecantruely "Let the Market Decide".
Under the current monopolistic medical system, anyone in the system (be it MD, hospital/HMO, health insurance company, drug company) can stick a gun in your ribs and say "Your money or your life." The ultimate in cohersive power (worse still, they have the same threat over your significant others and can hold them hostage too). This health care monopoly is what has allowed the cost of medical treatment to sky-rocket. If we ameliorated that monopoly by giving the public a viable alternative to the private system, the cost of medicine would come down to a more reasonable level. Competition, it's the American way. There are many comparatively inexpensive ways to encourage competition through the public health system. 1)Create many more medical schools and turn out many more doctors (as ewll as nurses). 2) Give them an incentive to work in public health by forgiveness of student loans. 3) Open up the current military hospital system to the general public (beef up the current hospitals by building additional wings, open up the Military Hospitals that have been mothballed,etc.) 4) Open up all those old TB sanitariums (that are tucked away in the sticks) and turn them into nursing homes for less expensive long-term care. 5) Subsidize Religious Hospitals where administering health care is still a humanitarian duty (a 'corporal work of mercy') instead of just another way to make a buck('fleece the sheep'). 6) The PUBLIC (read gov't subsidized) university system currently researches and develops drugs, GIVES them to private drug companies and then allows these drug companies to charge whatever the market will bear to the same public that paid for their development. Why not give these Public universities access to their OWN distribution system, a PUBLIC drug distribution system. Then the drugs and medical procedures that aren't patentable (or are 'orphaned')will have a way of making it to the market place in OUR lifetime. 7) With a Parallel Medical System, we'll have another choice, an alternative: If we need the supposed "Cadillac" of the Private Health Care System, we can go to a Private MD and take Name-Brand drugs. But, if all we want is a tune-up and a few simple tests (they'll only take a blood sample and send it to the lab anyway), or we have a cronic, incurable, condition that has been diagnosed for years and all we need is to renew a prescription, we can opt for the less expensive 'generic' Public Health MD who'll write a prescription the for less expensive 'generic' Public Health drugs in the lowly Public Health Care System. At least we'd have the choice. At least the market can truely decide. 8)Needless dupication? We'll need all those additional facilies if the terrorists have their way.

Bob Badour said at November 7, 2003 8:20 PM:


I have to admit I did not take the time to read all of what you wrote, but it seems to me you are only describing the thin end of the wedge.

Right now, the doctors do not have the power in US medicine; the insurance companies have the power. If you socialize medicine, bureaucrats will have the power. I suggest you take a long and careful look at the history of socialized medicine in other countries before adopting it for yours.

James Hill said at November 13, 2003 11:51 AM:

Remember Defibritide? Back in 1987 in Chicago I attended a Thrombosis conference. My first. This was also touted as a real breakthrough. I did not think the science was very strong. This agent was also from Italy. Some strange endpoints were used. Whatever happened to Defibritide?

Phillp Rotman said at November 16, 2003 2:47 PM:

I have not read the entire study, however, two important questions remain.
First of all, what was the increase in serum HDL after the five weeks in individuals receiving the synthetic HDL. The second question would be wqas any dramatic increase in HDL in serum responsible for the reduction in placque formation or would it be as significant over longer and more traditional methods, such as sessation from smoking, increasing Omega-3
and wine or grape derivatives etc. Anotherwards-what would be the relationship between traditional methods in reducing arterial placaque versus this group tested.

Phillp Rotman said at November 16, 2003 2:47 PM:

I have not read the entire study, however, two important questions remain.
First of all, what was the increase in serum HDL after the five weeks in individuals receiving the synthetic HDL. The second question would be wqas any dramatic increase in HDL in serum responsible for the reduction in placque formation or would it be as significant over longer and more traditional methods, such as sessation from smoking, increasing Omega-3
and wine or grape derivatives etc. Anotherwards-what would be the relationship between traditional methods in reducing arterial placaque versus this group tested.

Randall Parker said at November 16, 2003 4:15 PM:

Philip, Keep in mind that the big touted recent result with Lipitor (atorvastatin) was that it stopped plaque build-up. It did not reverse plaque build up. That warranted an NY Times story with all sorts of exciting proclamations from its maker and clinicians. So for a synthetic constituent component of HDL to reverse plaque build-up is quite a coup.

As for all the other things one can do to improve diet and get exercise: Yes, they are all good. Will they actually reverse plaque build-up? I'm not sure. There was one study that came out a few months ago where a combination of all the positive dietary factors were placed in a single diet that included eggplant, nuts, plant sterols, and some other stuff and, if memory serves, that worked as well as Lipitor. Maybe that diet would reverse build-up. I don't recall the details on it but have been meaning to go back and try to find it again.

As for serum HDL in this latest study: the ApoA-I Milano protein does not last as long as normal ApoA-I and so it might not have boosted serum HDL all that much. But before it was broken down it carted off cholesterol from artery walls.

George Neill said at November 17, 2003 1:23 AM:

Would treatments with this synthetic HDL allow me to ride my bicycle faster? I figure I have coronary plaque buildup since I was obese through most of mid life, but have lost 75 pounds over the last two years on the Atkins low carbohydrate diet, and now have a Body Mass Index of 23 (normal range) at age 59 with all blood test categories in the normal range. I ride my bicycle 20 miles a day in one and a half hours, averaging 15 mph. If my coronary plaque buildup was reversed with this synthetic HDL, would my circulation improve enough to improve oxygen to my muscles enough to maybe allow me to average 20 mph and therefore be able to ride with a better cycling club, for more years? My parents died of heart disease at age 80 and 82.

TOM said at November 24, 2003 8:35 AM:

Since I found out about this remarkable discovery I have being very intrigued by the results.
The problem I am facing is that I live in Toronto,Ontario Canada and I am very interested in trials in my area but nobody is responding to my emails.I am wondering If you can help me by giving me some information on hospitals in Toronto,Ontario that will be conducting this experiment. Thank you and expect you will respond at the earliest time available for your self.

Peter Broomell said at November 25, 2003 4:25 AM:

There are those of us who have very low HDL who have been working on all aspects to improve our numbers. Mine for instance has gone from 16 when first tested to 27 in 3 years. This is a significant improvement but still in the extremely low range. This of course puts me in the extreme risk for heart attack even though I have no other risk factors. And it also has implications for life and health insurance coverage. I would also be willing to get into studies to see if this kind of therapy would work for those who do not presently have heart disease. Imagine if we could treat those people who already know they are at danger because of low HDL. Preventive medicine is exactly what I'm doing now but this could be a powerful new tool. Insurance companies should be willing to jump on this therapy since prevention is cheaper than the high cost of coronary artery disease or heart attack treatment. If anyone knows about trials in the Jacksonville, Florida area please post a message.

Howard Crane said at December 3, 2003 2:25 PM:

If the introduction of synthesized HDL is truly capable of reducing plaque in the arterial system it has to be the greatest news of our time,-far greater than Iraq or getting rid of Bush. Think of the millions world wide who could benefit. If it's not another scam why isn't it making all the headlines!

catey banbandoo said at December 5, 2003 5:30 PM:

I am skeptical.

My patients with elevated HDL, some in the range of 100mg/dl (I think those are the correct units) continue to maintain the same total cholesterol levels more or less over the years. A recent study injecting apo a1 milano into patients right after a heart attack showed that a weekly infusion of about 3150 mg/70kg patient reduced intravascular plaque by 4-6% over 5 weeks. Not terrifically impressive, because after a heart attack most people drop their total cholesterol levels quite a bit, partly because it seems to be an anti-acute phase reactant. My patients with a HDL of 100mg/dl walk around every day with 5000mg of HDL, much of which is apo a1, so at the rate of 4-6% over a 5 week period these people's bodies would be running out of cholesterol after a few years.

While high HDL is clearly a sign of vascular health, it may be that the ability for one's body to make it is impaired by poor vascular health, and that giving HDL or its apoproteins, is of minimal actual benefit.

Bill Moye said at December 20, 2003 5:03 PM:

After reading comments from the Canadians, I am not sure that we should rush to embrace socialized medicine. In a capilistic society such as ours, the product will not be developed unless someone, principally the drug companies can make a lot of money. Insurance companies will not be willing to invest unless it can be proven that they can also benefit monentarily, it's a bureatic catch 22, if you will. It's a shame that the process can't move aggressively forward.
I would certainly be willing to participate in the study.

Ed Vanscoy said at January 10, 2004 11:36 PM:

Since hearing about APO P1 Milano, I have been trying to find out where I can go in Italy to get these injections, but no avail. It will take 5 years for the FDA to approve this product in the U. S. A. I'm sure that I could get these shot's now in Limone Sul Garda or in Milan. If anyone has info, please advise.

Ed Vanscoy said at January 10, 2004 11:45 PM:

I would like to know where I could go to get the APO A-1 Milano shots. I have tried to find info from, Limone Sul Garda, and Milan, Italy, but no info. It will be 5 or 10 years, before the FDA approves this drug in America. My arteries can't wait that long. Please advise if you know who to contact in Italy.

Web Reid said at February 22, 2004 9:43 AM:

I would think if this apo A-1 Milano is tested on people who are suffering from plaque in their arteries and have suffered MI or angioplasties, coronary bypass surgery and are now in relatively good shape should be test subjects or controls to see if it makes a difference in thier cholosteral build up. If it does then maybe it could be prescribed to all who are at risk, if budget or insurance allows.

Al Cohen said at February 28, 2004 11:00 AM:

Synthetic HDL mimics the bodies natural HDL which decreases as we age. We need to keep the balance we have at a younger age of the HDL levels to prevent problems. Drug firms in America would lose billions of profits on all the other drugs they sell you for this same problem. They will prevent a simple solution like Synthetic HDL from being approved by the FDA at all costs. BEWARE OF BIG CORPORATIONS!

vernita said at February 28, 2004 10:17 PM:

I would like to know how i can find out about these trials my father has major blocking and cant undergo surgery can anyone help me

Bernie Gignac said at April 8, 2004 10:53 PM:

I have had an angioplasty in my left cornary artery 18 years ago in London, Ontario and have been taking medication ever since to lower my cholosteral build up and thin my blood. At the time of my angioplasty I also had a 60% plaque build up in my right cornary artery, which I still have. I have not seen a specialist in years since Windsor, Ontario is so short of such personel. I would be interested in being a test person for this Apo A-1 Milano testing. How would I go about it in Southern Ontario ( Windsor, Ontario )? I would be willing to travel to London or Toronto for this trial.

Telsa Andurs said at April 11, 2004 6:28 AM:

I am 54 years and having problems with high colesterol. I had it at 230 for two years, I did not like taking the medication so now I am at 271.. I guess I am serious now.. I am taking my medication :Crestor twice daily. I purchsed a book on lowing your colesterol:Natural Ways To LOWER YOUR CHOLESTEROL, 30 points in 30 days.. I would be interested in any progam you might have or information. Please email me..

MALCOLM OWENS said at April 13, 2004 5:22 PM:


Lou said at April 15, 2004 3:25 PM:

I'm 61 years of age of southern italian extraction. Smoked for some 40 years, but ate well and exercised 4 times a week most of my adult life. Just recently had a positive thallium stress test. A "Taxus" stent was placed in my lad artery which showed 95% blockage. Other arteries are about 50% blocked and are being treated with medication. Total cholesterol was at 214 prior to the meds.

Vince said at April 16, 2004 8:02 AM:

I have been on a reversal diet and lifestyle change since 1998. I am interested also in trying Milano. I am grateful for any help.
Thank you

Lewis L. DeLand said at April 21, 2004 7:51 PM:

Being young with substantial plaque buildup throughout my coronary arteries, causing stroke, carotid artery surgery and heart angioplasty/stent implant, I would like to participate in a research study of the effects of the HDL injections. Who, what and where are these tests/studies and participants.

byron true said at April 29, 2004 8:07 PM:

dear sirs..just as many of the people above have expressed their wishes to be in a study of synthetic hdl to clear out plaque from heart and all parts of my body..of course i would enjoy entering an experimental study anywhere...i retired from an airline 39 years as a technician...transportation would not be a problem..

Darrell Buttshaw said at May 11, 2004 6:58 AM:

I am very interested being in the study for synthetic hdl. I live just one hour from Mayo Clinic in Rochester Mn. Will they be conducting any studies? After 4 heartatacks and triple bypass my left main and right main are 100% blocked. My doctors tell me I am not a candidate for surgery. I need this NOW. I can not wait.

Eugene said at May 20, 2004 3:03 AM:

Approximately 6 year ago, I was diagnosed with a 60% plaque build-up in the basilar artery. Although I am on coumadin medication, I recently began experiencing flashes of light-headedness. Consequently, I would like to participate in the synthetic HDL study as I believe it would help. I am willing to travel to any location as necessary. Please advise.

Terry Wolf said at June 8, 2004 9:14 PM:

Do you have any additional information on where to apply to be a patient in the new clinical studies for synthetic HDL? Are any west coast facilities doing clinical trials?

Lou said at June 13, 2004 7:50 PM:

I'm becoming skeptical about the validity of this site. I've not received any response, and it appears that others have not as well. I would hope that the webmaster would please respond to our emails. If not, then please remove this site so as to not foster false hope. Thank you.

Bob said at July 29, 2004 10:23 AM:

The reason you may not be hearing anything about this "wonder drug" is that in February or March of 2004 Pfizer bought Esperion. Amazingly, shortly after that all news ceased. There is nothing on their website about any of the four approaches Esperion was testing at the time. Why? Possibly because there is no long term money in a drug that cures the problem. What a world we live in!

R Anderson said at July 31, 2004 11:42 PM:

I am intriqued by this site as I look for a study to identify why I don't have plaque in my arteries.

I am not of Italian descent; but I have something in my blood that stops plaque from forming in my arteries. To make a long story short, I have very high tryglicerides >1700, high cholesterol >250, and low hdl less than

What I am wondering is could a pint of my blood (type B+) be given monthly to a person with plaque in his arteries and cause reversal of his CAD. I know this sounds simplistic but wouldn't it be cool if it would help someone in need.

J. M. West said at August 11, 2004 4:37 PM:

Any of you heard of Dr. Linus Pauling? He had the cure for heart disease 10 years ago, and has the only U.S. patent for the cure of cardiovascular disease. Go to the folowing link I hope this helps!

kate sisco said at September 8, 2004 11:43 AM:

Bless all libraries and the Bill and Malinda Gates Foundation!
Since I have been able to research the web through the library, I have seen much info available on just about any aspect of hardening of the arteries. I have seen info re Pauling and Vitamin C. Even at that time, he was cautioned that sugar in the blood will reduce the action of Vit C but I do take Vit C. I also take a B 50 which research indicated some of the B are good for heart conditions. I have seen a site which states the sugar that rots in the lower intestine and causes the candida to transmute into a deadly fungus that perforates the intestine and spills the undigested contents into the blood stream as the source of many immune disfunction diseases. More and more of what I read has pointed the finger at sugar.
I now believe I have had PVD for some 20 years, and the up to 300 chloresterol to go along with it. I also was reluctant to take statins due to the hype and the side effects. I was hoping to see the ap10 milano be released as an effective agent to up the HDL. I have also read the literature about nuts which I am more than willing to use despite the calories. And remember this recent news blip about cinnamon and now dark chocolate? I suspect all these things are good for us but they have an uphill battle against whatever is keeping our bodies off kilter, which may be sugar and how can we possible manage our dietary lives in this society without consuming sugar?
Remember that the sugar profits stem from early colonial days and I do not foresee any way these long term and entrenched profits are going to be sidetracked even if every single man, woman and child in the US develops diabetes. I believe this has already been tried re cigarettes whose profits did not envolve as many of as as sugar does.
We are unfortunately too common and easily replaced and therefore expendable for any global corporation to concern themselves with our fate at the hands of greedy commercialists.

Paul Prouty said at October 9, 2004 8:15 PM:

First, found the internet write-up by Esperion just before Pfzier bought them out and copied it along with one from Cleveland Clinic. I wrote Esperion a letter asking for possibly being included in research because it had gotten to where with bipass surgery, four stints around my heart, two in my femerol arteries so I could walk and two operations on my carateriod artery, I had become desperate. I got a reply from Pfizer because they had taken over Esperion. Quote"Esperion is not able to advise you on your health or your possible involvement in research protocols. Please talk with your physician---etc." Took everything to my physician and he got back the next day saying, this drug will never see the "Light of Day". When I asked him why, because it would put too many symtomatic drugs out of business, they can't let that happen because it would cost them billions.

Someone tell me I'm wrong!!!
Maybe I should write Chaney or Bill O'Reilly, he will take on anything.

Randall Parker said at October 9, 2004 10:01 PM:

Paul Prouty,

Most clinical trial enrollments are done throiugh clinics and research centers. Enrollments are usually not done by contacting the companies developing the drugs.

Also, when a company has completed a particular phase of testing they then switch over to submitting to the FDA to argue that the results are promising and that they should go on to the next phase. Since the FDA doesn't want companies blabbing a lot with patients it is my impression that the companies tend to be tight-lipped.

Try the Cleveland Clinic. In my experience the clinics usually have a person (frequently an R.N.) who fields phone calls about clinical trials. I've made calls into some major medical centers about their clinical trials for my family members and have usually been routed to someone who knows what they have coming up and what the eligibility requirements and demands would be for participation.

james said at December 7, 2004 7:04 AM:

It would seem to me that phizer would have no reason to speed the development of this new therapy since they have a major investment in the statin drug Lipitor. The only people that stand to benefit from the development of this new therapy are the cardiovascular patients that presently have partially blocked arteries. It also seems that cardiologists have no interest in the quick development since a major part of their business is angioplasty, stint installation and other procedures that I'm not aware of at the present time. Open heart surgeons are certainly not interested in seeing this procedure become a standard of medicine.

Your comments would be of interest to all cardiovascular patients.

Randall Parker said at December 7, 2004 11:24 AM:


Pfizer faces patent expirations for Lipitor in 2010 and 2011. So they need to get a new and better treatment available by then. A drug's time to market can be 5 or 10 years. So they would have to be trying hard right now to get to market by the time Lipitor's patent expires. So I do not see how they have an economic interest in doing nothing with this HDL cholesterol treatment.

anufa said at February 12, 2005 1:00 AM:

i read about milano mutant &i got quiete interested.
i am student of life sciences at masters level.
i want to present a review /seminar on this (and only this)subject at my institute
but i could not find out any recent review(which is free on net) which includes mechanism of action of this mutant .
please provide help!

Anthony Price said at March 22, 2005 11:08 AM:

I'm nervous about Pfizer, I understand that the patent on Lipitor is expiring soon, but they are nearing
the final stage of their HDL raising drug torcetrapib. I read that Pfizer is going to piggyback torcetrapib
with Lipitor: an LDL lowering/HDL raising/two for one. This sounds suspiciously like they are trying to
prevent torcetrapib from being available for people using any other statin except Lipitor. The fear is that
with the new Lipitor/Torcetrapib combo coming next, that Apo A1 Milano might just be put to the back burner.
Do you know if Pfizer is proceeding with clinical trials for Apo A-1? It is a great post, very thought
provoking. Can HDL of the right type (not the patented Apo A-1, just the type that might work) be purchased?
How and where? RSVP if you're still there. Thanks

Curtis Bufford said at June 3, 2005 7:31 AM:

My family has a history of very low hdl levels and high ldl levels. How long before this product becomes available for people like us. Is there any way that we can become part of your study group. My sister and I do not respond very well to the available medication to lower cholesterol. Thanks.

Mark Childs said at July 27, 2005 9:30 PM:

Please help me find a Pfizer email address I can give to my Heart Specialists concerning ApoA1 Milano. Thanks.
Mark Childs

Mark Childs said at July 31, 2005 6:06 AM:

I would like to be in one of these clinical trials as I have allready had two heart attacks please. Also Please send this information to Dr. Milne. at: Dr. Phillip A. Milne, M.D. Aloha Cardiology,LLC. 135 S. Wakea Avenue.
Suite #101. Kahului, Hawaii. 96732. (808) 871-8878 And Plese send this information to: Dr. Edward N. Shen, M.D.
F.R.C.P.(C),F.A.C.C.,F.A.C.P., Inc. Queens POB I. 1380 Lustana St. Suite 701. Honolulu, Hawaii.96813(808) 587-8200.
Thankyou Very Much
Very Sincerely
Mark Childs

Archie Mcgee said at August 12, 2005 9:27 AM:

My father had surgery last yr. age 57, he is doing O.K. but has low HDL and CVDisease so its only a quick fix not a cure. I am 37 and am apparently headed for the same fate, my Hdl is low at 38 points. I adjusted my diet and exercize at least 3 times a week this only took me to an HDL of 42.
I read a little about the Milano drug but was more excited about the direction Novartis is taking "D-4F" check it out at;
unfortunately it is only in phase I testing. At present it sounds like the best hope for people like us is Pfizer's Torcetrapib? If any one out there has a good direction to point me in I would be grateful to hear of it. I am happy to see that my children will be privy to these treatments before its too late. My daughter is 5yrs. old.

Archie Mcgee said at August 12, 2005 9:27 AM:

My father had surgery last yr. age 57, he is doing O.K. but has low HDL and CVDisease so its only a quick fix not a cure. I am 37 and am apparently headed for the same fate, my Hdl is low at 38 points. I adjusted my diet and exercize at least 3 times a week this only took me to an HDL of 42.
I read a little about the Milano drug but was more excited about the direction Novartis is taking "D-4F" check it out at;
unfortunately it is only in phase I testing. At present it sounds like the best hope for people like us is Pfizer's Torcetrapib? If any one out there has a good direction to point me in I would be grateful to hear of it. I am happy to see that my children will be privy to these treatments before its too late. My daughter is 5yrs. old.

Douglas Johnson said at October 27, 2005 7:25 AM:

Time for another update on ApoA-I Milano?

J. Glover said at October 28, 2005 1:23 PM:

I would also like to be in one of the clinical trials. In the past 3 years I have not been able to get my HDL above 32 no matter what I do or take... After two heart attacks, one at 37 and the other at 44 and six stents I will just about try anything....

Ed Saikaly said at December 6, 2005 5:34 PM:

I am interested in any therapy that would help increase my HDL levels. I have had over 20 angio plasties including stents, a quadruple bypass, and replacement of the aortic valve which also included a double bypass at the same time. I am now looking at a possible third bypass operation withing the next year.

If anyone can post any information about the status of Apo-A1 Milano licensing in Canada it would be appreciated. My cardiologist has little information on this subject. I am told that the drug is still about two years away from approval in Canada... not sure of the accuracy of this info. Can anyone please post more detailed information regarding the status of this drug. I am willing to participate in any study pertaining to the advancement of Apo-A1 Milano.

Thanks in advance for your help.

Bob Hearn said at December 12, 2005 6:04 PM:

I had 3 heart attacks, stents, and bypass and pacemaker/defibrolater. One of my 4 grafs is blocked and the others probably are narrowing. I'm experiencing past symptoms. Something to clear the arteries is a necessity. I would like to participate in further trials of the Synthetic HDL(ApoA1 Milano). I haven't been able to find a contact at Esperion or Pfizer. Please send me any contact information.

Bob Hearn

Paul Chernick said at December 26, 2005 5:06 AM:

up date to discussuion on HDL . have trouble getting my ldl cholesterol down below 80 to reverse artery blockage( currently on lipitor (40 m) and Zeita (10) and just re read article on milano hdl trials. any updates after esperion bought by pzsier. also does any one know about this product/medications or any others ? 8-Day-Total-Cleanse - Vegetable Broth flavor - includes 1 Canister Seven Essentials™, 2 Bottles Aloe7000™, 1 BottleCleansingEnzymes, 1 Bottle Parasite Cleanse, ph Tape & Instructions
Thanks love to hear the latest info . have a happy Holliday.

Johan Human said at February 3, 2006 11:06 PM:

Is there anybody out there that can give a status on Apo-1 Milano, whether trials have been completed and what the situation is? Also a despoerate patient and there is simply no information forthcoming

Johan Human

Steve Redmond said at March 2, 2006 8:00 PM:

There was a recent story in USA today that gives some updates. Seems as though there are several companys working on this Apo-1 Milano. Cedars-Sinai Heart Center is working on a one time treatment that enables the body to produce its own Apo-1 Milano lipid on it's own. This has been around a long time as far back as October 1994 60 minute segment. I would hope for all of us that with the differnt companies working toward a new drug that competition will force it to market soon. I would guess that the market would be huge and lots of money to be made thats always a movtivator.

John Messager said at March 14, 2006 8:30 AM:

All kinds of postings enquiring about ApoA1 Milano but, no info! Does anyone out there have any updates on when it will be available to the public?

Samuel Weber said at April 16, 2006 11:20 AM:

Still looking for any new postings about the availability of ApoA-1 Molano. Anyone have any updates on when it will be available to the public?

James Lewis said at April 30, 2006 1:55 AM:

[Edited by moderator because the poster pasted in an entire article which was copyrighted material]

Local heart attack patient participates in clinical trial

06:27 PM EST on Thursday, January 26, 2006


A Charlotte man is one of the first patients to receive a new medication that could treat heart attack victims.

Doctors at Mid Carolina Cardiology are treating the first heart attack patient in a clinical trial for what may be a groundbreaking drug. Their hope is to clear arteries blocked with cholesterol without surgery.

The story of the new drug actually begins 30 years ago in a small Italian town called Milano. Doctors there found about 40 people in one family who were living very long lives with few heart attacks or strokes. The reason was a genetic defect that helped their bodies get rid of the bad cholesterol that triggers heart attacks.

Bill Thompson said at May 15, 2006 10:40 AM:

To those expressing an interest in participating in a clinical study for synthetic HDL you might contact Sunnybrook Hospital located in Toronto, Canada. They currently are conducting a study called ERASE. It is my understanding they are looking for participants.

Paul Henderson said at June 4, 2006 8:35 AM:

I look with suspicion when Phizer buys a new drug that might fix arterial problems. It's the bootm line that controls here, and Phizer wont put this drug on market until it fully exhausts its money makers now in vogue.

The Milano drug seems to do the same thing as does EDTA chelation which has been around for many years. It was first used to detoxify lead in humans, and then it was found to have improved arterial disease among others. However, its patent ran out, so the drug companies can't make money on it. It's approved by FDA for metals poisoning treatment, but not for arterial or other uses. To get FDA approval would cost $$$$ mucho, so no one wants to pay for something that they can't patent Do some research on the net for EDTA chelation. You will be pleasantly surprised at what you see. There's an excellent book by Dr. Morton Walker, on Chelation Therapy which any heart patient should read.

Bogaert said at August 2, 2006 12:49 AM:

Does Pfizer comment somewhere on the development of this drug( Apo1 Milano).I am waiting for it desparately.

Joe said at October 6, 2006 11:40 AM:

During my recent yearly complete physical, my physician told me that my LDL was 110, my Triglicrides are 127, and my HDL leve was 33 much too low.

I am 65 years old male. My father family was from norther Italy my mother family was north of Rome but I do not know exactly.

I am extremely active skiing, swimming and bicycling, walking etc. I feel fantastic.

However my physician was to to take NIASPAN to bring up my level of HDL to a more acceptable.

I want to change my diet and start taking a natural cure -vitamins etc., because I am very concerned about the problems associated NIASPAN and other cholestrol medication to get my numbers in line.

What do you think!

Bob Martin said at October 12, 2006 11:18 AM:

A checkup several years ago confirmed my suspicions that I was suffering from cardio vascular disease at 57. My blood work revealed a total cholesterol level of 192, LDL 111, HDL 27, Trig 258. A followup angiogram showed 1 total, and one partial blockage. Doctors decided not to insert stents since the main coronary artery had only minor plaque buildup. Prescribed Lovastatin for one year did not improved the numbers at all. I discontinued the statin and started taking flush free niacin (inositol hexanicotinate 500mg) for 6 months. With no diet or weight change, the total cholesterol and LDL dropped almost 20%,however HDL and trig did not improve. I tolerate exercise better with less angina, so I am at least holding the line. No combination of exercise, nutrient supplements, diet or abstinance from any foods seem to affect my HDL level, which I feel is critially low, and probably an inherited familial trait (father/brothers with CHD).

I have a great interest in Torcetrapib, but have not had any luck locating trials in the Boise, Idaho area. I also can't find any information other than the typical blogs, regarding the projected release date of the drug.

Anyone have better information?
Bob Martin

Tom Kara said at October 14, 2006 8:38 PM:

I would suggest that the people on this board who want to raise their natural HDL consider standard niacin therapy (not "flush free" niacin.) This is an old and established therapy. Apo-A1 Milano may or may not be any more effective than regular HDL that your body can make. There is a prescription form of niacin called Niaspan which is designed to release slowly and avoid some of the side effects (flushing, which is harmless, although some people also get mild palpitations - but side effects tend to decrease dramatically with time). However, I was not happy that Niaspan doses are so high. My cardiologist in St Louis prescribed regular OTC niacin (again, not "flush free" which is something else again - niacin bound to inositol). I began taking 50mg with food at night, gradually increasing it to 500 mg each night. You can get regular niacin through reputable mail order supplement companies such as Puritans Pride. My HDL skyrocketed from under 40 to over 70. (last test was HDL 71, LDL 89, triglycerides 55). I'm now on 625 mg (the tabs come in 250mg strength, so I take 2 1/2 tabs with food at night). I get very little, if any, flushing now, and my liver enzymes are normal. You should do this under a doctor's supervision so that your liver enzymes are checked. Many doctors seem to think you need much higher doses of niacin to be effective (up to 3000mg per day) but this is simply not true. Start with a lower dose, and once you get to 500mg per day your lipid panel should be done to see how your HDL and LDL are doing. If you need more, you can then increase it to 750mg or 1000mg or higher if necessary. My cardiologist also recommended 3 grams of fish oil per day. This effectively lowers triglycerides, and also helps prevent clotting, and I believe is antiarrythmic. Why aren't you hearing about these old and very cheap medical remedies? Guess - there's no money in them. And too many doctors are pushing the latest patented stuff - I often hear of people being put on both Niaspan and statin drugs. I refuse to take statin drugs - if you want to know why, do a Google search of "statin side effects". Statin drugs don't raise HDL which is why they're trying to patent drugs that do. Take charge of your health. If your doctor resists, tell them you want to try niacin and fish oil for three months. If they still resist, find a new doctor! An excellent book that discusses all of this is "The Heart Disease Breakthrough" by Thomas Yannios, MD. Try Amazon or a good library.

DR GUS SAMAHA said at January 13, 2007 10:54 PM:


woody voinche said at February 14, 2007 8:28 PM:

Please contact me if new trials start with ApoA1 Milano treatment

j handal said at October 26, 2007 4:23 PM:

i have read that pfizer plans to NOT produce apo-1 milano hdl variant. the reason is that it would "cost too much" and people would not buy it. right? millionares wouldn't pay $10 or $20,000 or more to unblock all his arteries? really? so the question is .. how did they decide to buy a one product company for a product and then decide it was too expensive to produce. due dilligence, it seems means ... "let's buy the cure or pfizer won't be able to make money on sustainment drugs like lipitor" if someone on this bullleten board knows media people, let's expose pfizer for violating the intent of the patent laws and acting against the public good; they should either produce etc-216 or put the pattent in the public domain.

larry mophinome said at November 20, 2007 12:32 AM:

J handal,
where did you read that Pfizer is not going to produce etc-216?
I want to read the article

Fmulhare said at November 26, 2007 12:40 AM:

Jhandal- I totally agree with you about Pfizer and ETC-216.Why cure a disease when you can make more money by selling drugs that barely manage it. This is the downside of capitalism where the only incentive is to make money and not act for the greater good. I find it very difficult not to believe that Pfizer is slowly killing this drug so it can continue to sell statins. I do not know anyone in the media but I sure wish I did.

Kevin McCarthy said at November 29, 2007 5:18 PM:

Comments from last November's Pfizer analyst's conference:

"And then just clarification on your Esperion compounds
-- you'd be going into phase IIB with both the mimetics and
then the Milano as well?
JOHN L. LaMATTINA, PhD: So reverse order. Esperion,
yes, we would go into phase IIB studies with both
compounds, assuming they pass the obvious hurdles. ETC-216
is the one that's furthest along".

"JOHN L. LaMATTINA, PhD: And I'll comment on one more,
and that's the Esperion compounds because I suspect others
have questions on that as well.
The Esperion -- we're still excited about the Esperion
compounds. They're moving forward. One of the issues that
we faced in that program was that the -- a small biotech
company like Esperion doesn't necessarily have the
resources to do all the things that are needed to get
things ready for long-term trials.
The synthesis and the analytics around the material
that came out that they had available to them at that time
really weren't robust enough for us to be able to start
phase III. So we've had to go back and do a lot of work
around that.
I think we've pretty much figured that out and solved
those problems, so those compounds we hope to move into
phase -- key phase IIB studies in the next year".

gk said at May 7, 2008 7:41 AM:

We've heard Doctors saying that APO A1 MILANO i.e. etc216 shall be sure success but why is the launch being delayed? Nor the Pfizer company or other Health Associations are making anything clear. A drug like this is a boon to mankind even then no organization is keen to know, launch and start treatment for people waiting for tedious bypass surgery. If any one have news kindly post.
Thanks, god bless!

Gene Isaac said at February 6, 2009 1:53 AM:

ROCKVILLE, Maryland – May 8, 2008 – Human Genome Sciences, Inc. (Nasdaq: HGSI) today announced that John L. LaMattina, Ph.D., who retired in late 2007 as President of Pfizer Global Research and Development, has been appointed to the HGS Board of Directors.

“We are honored to have John LaMattina join our Board of Directors,” said H. Thomas Watkins, President and Chief Executive Officer, HGS. “John’s record of accomplishment over the course of a 30-year career at Pfizer has established him as one of the pharmaceutical industry’s outstanding worldwide leaders of research and development. In particular, he played an important role in growing Pfizer’s pipeline in oncology and guiding its investment in biologics and vaccines. We view the HGS oncology program as a key driver of future growth beyond our late-stage products, and we look forward to benefiting from John’s experience and insight as we continue our strategic investment in our pipeline.”

As Senior Vice President, Pfizer Inc., and President Pfizer Global Research & Development, Dr. LaMattina led the Pfizer’s drug discovery and development efforts in the United States, Europe and Asia. He joined Pfizer in 1977 and over the years held positions of increasing responsibility for Pfizer Central Research, including Vice President of U.S. Discovery Operations, Senior Vice President of Worldwide Discovery Operations and Senior Vice President of Worldwide Development.

Dr. LaMattina graduated cum laude from Boston College, and received his Ph.D. in organic chemistry from the University of New Hampshire, where he worked with Professor Robert E. Lyle. He then moved on to Princeton University as a National Institutes of Health Postdoctoral Fellow in the laboratory of Professor E. C. Taylor. Dr. LaMattina received the 1998 Boston College Alumni Award of Excellence in Science, and received an Honorary Doctor of Science degree from the University of New Hampshire in 2007.

Dr. LaMattina serves on the Board of Directors of the Neurogen Corporation and the Board of Trustees of Boston College.

Noni said at March 15, 2010 10:19 AM:

Bad news, Pfizer decided to drop the study on Apo A-1 in Dec 2009.
Good news is Pfizer sold the patent to Medicines Company.

We hope that Medicine Company will do the best to have the drug on market soon.

Anonymous said at February 4, 2012 4:34 PM:

Medicine Company announced in November 2011 of some good pre-clinical efficacy data. Seems they have had some of the same issues that Esperion and Pfizer had which was just being able to scale up production.

A private company, Cerenis is probably the farthest along, although they are using the wild type sequence of apoa-1 and not Milano.

In terms of Apoa-1 Milano, others to keep an eye on include Cardigant Medical out of Los Angeles and Sembiosys out of Calgary, Canada.

Hopefully this therapy will come to market as it does seem to have solid potential.

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