2006 October 01 Sunday
Drug Mobilizes Cells For Stroke And Heart Disease Recovery

The experimental drug AMD3100 mobilizes cells responsible for the growth of new blood vessels (angiogenesis) and could reduce the extent of lasting damage after a stroke or heart attack.

Recently, researchers at Washington University School of Medicine in St. Louis demonstrated that a drug called AMD3100 can mobilize angiogenic cells from bone marrow of human patients in a matter of hours instead of days, as was the case with a related agent called G-CSF.

Angiogenic cells reside mainly in the bone marrow, and when mobilized they can circulate in the bloodstream, homing to sites of injury and helping repair and regrow blood vessels that bring oxygen and nutrients to tissues.

"Like AMD3100, G-CSF can bring these beneficial cells from the bone marrow into the bloodstream, but with G-CSF you don't see an increase in angiogenic cells until the fourth day," says senior author Daniel C. Link, M.D., associate professor of medicine in the Division of Oncology. "In a patient who has had a heart attack, that may be too late. In fact, two clinical trials of G-SCF found the treatment doesn't improve recovery from heart attacks."

In an article in the journal Blood, the researchers showed that AMD3100 caused a 10- to 20-fold increase in certain angiogenic cells in the blood within four hours in human subjects, suggesting the drug could be a more effective treatment for heart attack or stroke.

Harvard Medical School researcher Judah Folkman MD has achieved reknown for his research into anti-angiogenesis compounds to block growth of blood vessels in tumors. Cancer cells develop mutations that cause them to excrete angiogenesis compounds which stimulate blood vessel growth. But as with so many other biological processes, things that cancer cells do can be very beneficial when done by cells which are not cancerous.

Drugs like AMD3100 fit into an even larger category than angiogenesis stimulation. More broadly AMD3100 is yet another compound that stimulates one of the many processes needed for growth and repair. To do rejuvenation we need the ability to turn on (and eventually off) every biological process that produces cells and repairs damage.

By Randall Parker    2006 October 01 11:11 AM   Entry Permalink | Comments (0)
2006 September 28 Thursday
Apo A-I Milano Better HDL Cholesterol

In Milan (or as the Italians say, Milano) Italy some people have a mutation of high density lipoprotein (HDL) cholesterol called Apolipoprotein A-I Milano which is suspected of reducing the risk of heart and cardiovascular disease. In order to investigate whether Apo A-I Milano really does reduce risk of cardiovascular diseases researchers at Cedars-Sinai put human variations of HDL choelsterol into mice and then measured the resulting mice. While normal human HDL cholesterol reduced plaque build-up by 25% the Apo A-I Milano version of the gene reduces plaque build-up by 65%.

LOS ANGELES - Transfer of a gene that produces a mutant form of good cholesterol provides significantly better anti-plaque and anti-inflammation benefits than therapy using the "normal" HDL gene, according to a mouse study conducted by cardiology researchers at Cedars-Sinai Medical Center and reported in the Oct. 3 issue of the Journal of the American College of Cardiology.

Apolipoprotein A-I is a naturally occurring component of normal HDL (high-density lipoprotein), the "good" cholesterol that circulates in the blood stream. Apolipoprotein A-I Milano is a mutant form, which was originally found in a small number of individuals in Italy who appear to be protected from cholesterol-related heart disease. Researchers are studying the possibility of treating vascular inflammation and plaque buildup through the transfer of protective genes.

"There has been uncertainty and controversy about whether apo A-I Milano is a better form of HDL than the "wild type" (regular) apo A-I in terms of protective effect against atherosclerosis and vascular inflammation, which are tied together," said Prediman K. Shah, M.D., director of the Division of Cardiology and the Atherosclerosis Research Center at Cedars-Sinai.

"We used a unique approach to do a head-to-head comparison, which allowed us to conclusively ascertain the differences between the two genes. Our study demonstrated that A-I Milano gene transfer is much more effective in reducing plaque and vascular inflammation than the normal (wild type) form of apo A-I," said Shah, the article's senior author.

Compared to control, wild type apo A-I gene transfer led to about a 25 percent decrease in the amount of plaque buildup in the animals' aortas and other vessels. Apo A-I Milano gene transfer resulted in a 65 percent reduction. The amount of gene product (protein) produced by each gene was identical, measured in the blood and in the plaque.

A gene therapy that converted our livers to make Apo A-I Milano HDL cholesterol would likely reduce both inflammation and the rate of accumulation of damage from oxidation and plaque build-up in the circulatory system. My guess is such a treatment would reduce the amount of free radicals in the blood and therefore also reduce the rate of brain aging.

Drugs that raise the concentration of HDL cholesterol will hit the market many years before a gene therapy that converts our bodies to make Apo A-I Milano HDL. We might also see clinical use of intravenous administration of Apo A-I Milano HDL as a way to get a bigger and quicker benefit, especially for those suffering angina. Also see my post Synthetic HDL Cholesterol Reduces Artery Clogging In 6 Weeks.

By Randall Parker    2006 September 28 11:23 PM   Entry Permalink | Comments (9)
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