Roanoke Times
Copyright (c) 1995, Landmark Communications, Inc.
DATE: TUESDAY, April 26, 1994 TAG: 9404260137
SECTION: NATIONAL/INTERNATIONAL PAGE: A3 EDITION: METRO
SOURCE: Newsday
DATELINE: LENGTH: Medium
Researchers said new tests in rabbits show that thalidomide strongly inhibits the abnormal growth of tiny blood vessels in the retina, a vital filmlike structure at the back of the eye that serves as a light-sensing organ.
The growth of tiny blood vessels, capillaries, researchers said, is a source of damage that leads to diabetic retinopathy, which affects 1.2 million dto's results ``seem very promising. It looks like a really big boost in that area'' of eye research. Brooks is also studying ways to block abnormal blood vessel growth, a phenomenon known technically as angiogenesis.
Thalomide appears to cut abnormal capillary growth by nearly half, tending to shiled the retina from damage, the researchers said. Opthalmologist Robert D'Amato and his colleagues, working with Dr. Judah Folkman at Children's Hospitalin Boston, reported their results Monday in the Proceedings of the National Academy of Sciences. D'Amato said they expect to soon begin clinical trials of thalidomide in persons at risk for the eye disorders. Biologist Peter Brooks, at the Scripps Research Institute in California, said D\Amato's results "seem very promising. It looks like a really big boost in that area" of eye research. Brooks is also studying ways to block abnormal blood vessel growth, a phenomenon known technically as angiogenesis. Although thalidomide has a terrible reputation, having caused birth defects in thousands of babies in Europe in the 1960s, D'Amato said it seems to be safe - except when taken by pregnant women. It is so benign, in fact, that ``you can't overdose on it, it's so nontoxic.''
He believes birth defects were caused by the same mechanism that may be useful against eye disorders: thalidomide's ability to block blood vessel growth. By stopping the growth of new blood vessels when fetuses were trying to grow arms and legs, normal development was interrupted. The babies were born with flipperlike appendages in place of arms and legs.
Although ``the mechanism by which it [thalidomide] caused birth defects is unknown, my view is that it contributed'' by interfering with blood vessel growth. This seems likely, he said, because ``angiogenesis is critical for limb development.''
The key to such research was Folkman's discovery 30 years ago that abnormal blood vessel growth plays a key role in allowing malignant tumors to grow and spread. He has since found that other disorders also involve abnormal blood vessel growth. That is now being exploited in the diagnosis and treatment of several forms of cancer, eye disease and tumorlike growths called hemangiomas in babies.
Because of the dangers of birth defects, D'Amato said, the proposed thalidomide trials will be done only in men and postmenopausal women.
The test will be sponsored by a biotechnology firm, EntreMed Inc., of Rockville, Md.
(Optional add end)
When thalidomide was introduced commercially in Europe in 1957 as a safe and effective sedative, it led to an absolute disaster. A rare congenital condition in newborns, phocomelia - flipperlike limbs - began to appear in West Germany, and soon reached epidemic proportions as hundreds of cases were reported in much of Europe, Britain, Canada, Australia and elsewhere.
After a baffling three years, pediatrician Widukind Lenz, at Hamburg University, placed the blame on thalidomide, prescribed to ease morning sickness in expectant mothers. The drug was pulled from the market on Nov. 26, 1961, although in Canada it was still sold until March 1962.
Fortunately, thalidomide was never marketed in the United States - although it had been distributed to some doctors for experimental use. The U.S. Food and Drug Administration had withheld approval - despite strong pressure from the manufacturer - because not enough tests in different animal species had been done. As it was being studied in the United States, thalidomide's link to birth defects was discovered.
The danger had escaped notice in Europe because thalidomide was tested only in rats and mice, which lack a natural liver enzyme that cuts thalidomide molecules, producing a chemical that does the damage. Rabbits and humans do have that enzyme, and birth defects were the result.
by CNB