By William J. Cromie

Gazette Staff

Mr. D. had been an active middle-ager. But in his 60s, he began to experience sudden drops in blood pressure. D. felt faint when he stood up, and he broke his arm in a nasty fall. Now, D. approaches his 70th birthday, he can't get out of a chair or bed without help.

D. suffers from autonomic failure, progressive deterioration of the nervous system that controls such involuntary but vital functions as heartbeat, blood pressure, breathing, and bowel and bladder functions. It is common among elderly people and happens to younger people with a variety of diseases including diabetes, Parkinson's, and some less-well-known maladies. When left untreated, it leads to loss of consciousness, serious falls, heart attacks, strokes, and inability to stand.

"Autonomic failure is a very tough disease that kills and devastates the lives of thousands of people," says Roy Freeman, assistant professor of neurology at the Medical School. "Without treatment, every vital function eventually stops working."

On Tuesday, at a meeting of neurologists in Boston, Freeman reported on the results of experiments at Beth Israel Deaconess Medical Center that hold promise for treating the symptoms of autonomic failure and extending the lives of its victims.

Freeman and his colleagues found that a drug called DL-DOPS prevents the sudden, severe drop in blood pressure suffered by these patients after eating and when they stand up. The drug is a relative of L-DOPA, the most effective treatment to date for Parkinson's disease, a brain disorder with many of the same symptoms as autonomic failure.

Tilting the Table

Blood pressure normally rises slightly when people stand up in order to assure a blood supply to the brain. But in those suffering from autonomic failure, blood pressure can drop so dramatically it can't be measured.

Freeman took a dozen such people and gave half of them DL-DOPS. The other half took a dummy pill. Then he switched who got what. So no one would fall down, he strapped them to a tilt table in his lab and raised the table from a horizontal to a vertical position.

Those who took the drug did much better than those who got the placebo. "There was overwhelming improvement in the first group," Freeman says. "The dizzying drops in blood pressure were prevented, and no one suffered unwanted side-effects."

Previously, he and his colleagues got similar results with 11 patients who took DL-DOPS or a placebo before they ate.

Normally blood pressure isn't changed by eating, although it may drop slightly in elderly people. But a meal can cause a sickening drop in those with autonomic failure. When patients took DL-DOPS after a balanced meal, which included protein, carbohydrate, and fat, their pressure stayed closer to normal than the pressure of those who took placebos.

Freeman and others say they are "pretty convinced" that DL-DOPS works by replenishing the hormone norepinephrine. Secreted by certain nerve endings, norepinephrine helps to maintain blood pressure by constricting blood vessels when pressure falls below normal. When you stand up, it prevents blood from draining from your brain and upper body.

DL-DOPS serves as a chemical source from which the body makes norepinephrine when not enough exists naturally. In the same way, L-DOPA is converted into dopamine, the lack of which produces the muscle tremors and rigidity of Parkinson's.

Freeman decided to try DL-DOPS when he learned that neurologists had used it successfully to treat cases of Parkinson's and other diseases that involve lose of ability to make enough norepinephrine. A significant number of Parkinson's patients lack norepinephrine as well as dopamine.

The experiments done by Freeman were supported by the Orphan Drug Products Act, which funds development of drugs for illnesses not common enough for pharmaceutical companies to profitably invest in. No commercial source for DL-DOPS exists in the United States, so Freeman bought the drug from a chemical company. That entails the additional problem of checking the purity of the material before giving it to patients.

Freeman plans to do a larger study that will test DL-DOPS on many more people. His biggest obstacle is the high cost of the chemical, which is no longer made in the United States.

He may get some help from the National Aeronautics and Space Administration (NASA). Astronauts who spent months floating weightlessly aboard the Russian spacecraftMir experienced a condition similar to people with autonomic failure when they tried to stand up on Earth. Their hearts had been deconditioned by a lack of need to pump blood against the pull of gravity, so blood drained from their brains and pooled in their legs. The last astronaut to return from a four-month stay aboard Mir agreed to be taken off the space shuttle in a wheelchair. NASA needs to solve this problem because many more long flights are scheduled aboard Mir and aboard a planned new international space station.