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"Defective" But Beneficial Gene May Bring About Novel Ways To Clear Arterial Plaque Buildup

Date:
February 17, 2000
Source:
Cedars-Sinai Medical Center
Summary:
Members of a family from Limone, Italy, have been virtually immune to cholesterol-related heart problems and strokes, thanks to a mutant gene discovered in the 1980s. This mutant gene, referred to as the apolipoprotein A-1 Milano gene, and commonly shortened to apo A-1 Milano, may lead to major changes in the prevention and treatment of clogged arteries that lead to heart attacks and strokes. Limited human studies are expected to begin at Cedars-Sinai Medical Center during the second or third quarter of 2000.

Cedars-Sinai Medical Center Researchers Anticipate Human Clinical Studies

LOS ANGELES (February 11, 2000) – A mutant gene discovered in the 1980s in family members from a small town in Italy may lead to major changes in the prevention and treatment of clogged arteries that lead to heart attacks and strokes.

Limited human studies using the unique protein produced by this gene are expected to begin during the second or third quarter of 2000, according to cardiology researcher P.K. Shah, M.D., director of the medical center’s division of cardiology. Another study using the gene itself is also anticipated in the future.

Members of a family from Limone, Italy, have been virtually immune to cholesterol-related heart problems and strokes, even if they engaged in lifestyle practices such as smoking and overeating that normally lead to increased risk. Drs. Cesare Sirtori and Guido Franceschini of the University of Milan identified the gene, referred to as the apolipoprotein A-1 Milano gene, commonly shortened to apo A-1 Milano.

Although the gene was discovered in the 1980s, whether it protected arterial walls from plaque build-up was not known until several years ago. In 1992 Dr. Shah and his colleagues began studying the protein produced by this gene, apo A-1 Milano, a variant of the normal protein called apo A-1, which is a component of HDL or “good” cholesterol in animals. Over the past six years, Dr Shah and his colleagues have demonstrated that apo A-1 Milano is extremely potent in reducing plaque buildup in the arteries of rabbits and mice.

The gene’s discoverers and Dr. Shah are collaborating with the biopharmaceutical industry, to try to bring apo A-1 Milano protein into Phase I clinical trials later this year. If these studies are as successful as expected, larger-scale human studies would begin shortly thereafter.

Because the protein appears to actually remove bad cholesterol, even from sites on arteries where plaque has accumulated, the need for such invasive procedures as angioplasty and bypass surgery could someday be virtually eliminated – assuming similar benefits are seen in human studies. And because apo A-1 Milano treats the entire circulatory system, it may be useful in repairing diseased vessels that currently cannot be reached by invasive techniques.

In the meantime, Dr Shah and his colleagues, working together with scientists at City of Hope National Medical Center in Duarte, Calif, are also making attempts to insert the gene itself into the tissues of animals in a five- year study funded in part by a grant from the National Institutes of Health. “In this particular study, we are using the gene itself, not the product of the gene but the actual DNA that produces the protein,” said Dr. Shah. “Essentially, we want to put this gene inside the body of animals and get their tissues to produce the protein and to provide a continual supply of the protein.”

Dr. Shah said that once human studies are launched, these approaches may be first tested in patients who have a genetic disorder that causes their “bad” cholesterol levels to rise uncontrollably. Patients with this type of hypercholesterolemia often suffer heart attacks or require heart bypass surgeries even during their teen-age years. Although a new treatment called LDL apheresis is now available at Cedars-Sinai and a few other sites in the country, this mechanical method of “filtering” the bad cholesterol out of the blood requires ongoing treatments and associated inconvenience and expense.

Even without a genetic predisposition to high cholesterol levels, many patients fail to respond to current interventions and may be potential candidates for these novel techniques.

“Using very powerful lipid-lowering medications, aspirin, and lifestyle changes such as improved diet and exercise, we can prevent maybe 30 to 50 percent of heart attacks and strokes. But the other 50 to 70 percent of heart attacks continue to occur in spite of our best efforts. The potential of these new approaches is to further reduce the heart attacks that currently go unprevented in the average population, and to provide a potential treatment for people who have nothing but LDL apheresis to look forward to,” said Dr. Shah.


Story Source:

The above story is based on materials provided by Cedars-Sinai Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

Cedars-Sinai Medical Center. ""Defective" But Beneficial Gene May Bring About Novel Ways To Clear Arterial Plaque Buildup." ScienceDaily. ScienceDaily, 17 February 2000. <www.sciencedaily.com/releases/2000/02/000216082501.htm>.
Cedars-Sinai Medical Center. (2000, February 17). "Defective" But Beneficial Gene May Bring About Novel Ways To Clear Arterial Plaque Buildup. ScienceDaily. Retrieved September 23, 2014 from www.sciencedaily.com/releases/2000/02/000216082501.htm
Cedars-Sinai Medical Center. ""Defective" But Beneficial Gene May Bring About Novel Ways To Clear Arterial Plaque Buildup." ScienceDaily. www.sciencedaily.com/releases/2000/02/000216082501.htm (accessed September 23, 2014).

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