`Awakenings' Drug Is Only The Beginning

The movie ``Awakenings'' shows the miraculous effects of the drug L-dopa. For 30 years, a brain infection caused the main patient character, played by Robert De Niro, to languish in a coma, only to awaken after a doctor gave him L-dopa.

For the half a million Americans with Parkinson's disease, L-dopa can be nearly as dramatic in relieving their physical symptoms - the slow shuffling gait, the persistent trembling, the bouts of paralysis. These patients lack a key brain chemical, dopamine, which is replaced by the drug.

But as a treatment for Parkinson's, L-dopa is hardly miraculous. As the symptoms worsen, higher doses of the drug are needed. After about four years, the increasing doses cause significant side effects in about half the patients, limiting its benefit.

That's why scientists have been searching for alternate drugs to slow the progression of symptoms and even prevent the disease from developing in the first place.

``We think people have the disease five, 10, 20 years before they get the symptoms,'' said neurologist J. William Langston, president of the California Parkinson's Foundation. If patients could be identified early in their illness, he said, drugs now emerging from the laboratory may one day be able to slow or prevent it.

Last month, researchers at Schering AG, a pharmaceutical company in Berlin, reported in the British journal Nature that three new drugs were found in animal experiments to protect the brain from the effects of chemically induced Parkinson's disease. The new drugs clog proteins that open gateways into the nerve cells, preventing the Parkinson's-causing chemical from harming the nerve.

The next step is to test the drugs in human patients. While the animal tests are promising, scientists are cautious about human use of these drugs, which are known to cause memory loss.

``All of a sudden, this field is

moving forward,'' said Thomas Chase, chief of the National Institute of Neurological Disorders and Stroke's experimental therapeutics branch.

The first drug to emerge from this research explosion is deprenyl, now used as standard therapy for Parkinson's disease. Discovered 30 years ago, deprenyl prevents a normal brain enzyme from destroying dopamine and thus protects the dopamine-producing cells.

Last year, a large, federally financed study showed that deprenyl can slow to some extent the deterioration caused by Parkinson's. If doctors gave them the drug in the early stages of their disease, severe symptoms requiring L-dopa treatment were delayed an average of 18 months, compared with patients who did not get deprenyl. ``Deprenyl is a major step forward,'' Chase said.

Another drug that works much like deprenyl but seems even more potent is being tested in 200 patients in 14 research centers. The drug, made by Hoffmann-La Roche Inc., blocks the same enzyme as deprenyl. If results are encouraging, a Hoffman-La Roche spokesman said, the company will launch a larger trial to test the drug's effectiveness.

All of these drugs point to the strategy of early intervention to stop the disease before it develops into an incapacitating illness. The problem is identifying people who will succumb to Parkinson's.

``If we could find them, we could give them deprenyl (or some other drug) and perhaps prevent the disease from ever showing up,'' said Langston.

Last December, scientists on the Parkinson's Epidemiology Research Committee, a confederation of Parkinson's experts, reviewed several new developments that could lead to a quick diagnostic test.

William Parker Jr., a researcher at the University of Colorado Health Sciences Center in Denver, recently discovered that Parkinson's patients appear to have a defective enzyme in their platelets, the blood element involved in clotting. Other scientists have found the same defect in other tissues of the body, including the brain. If that enzyme turns out to be a marker for Parkinson's, a blood test could be developed to detect the disease.

Researchers also have found liver abnormalities in some patients with Parkinson's. The liver breaks down most of the toxic chemicals that enter the body. If a defect prevented the liver from destroying some chemical that kills brain cells, then the chemical could persist in the body long enough to cause Parkinson's disease.

Increasingly, researchers suspect that some chemical or chemicals in the environment - natural or synthetic - get into the body and accelerate the destruction of the dopamine-producing cells.

The environmental hypothesis received a boost in 1983 when some California drug addicts developed a severe form of Parkinson's after injecting a synthetic form of heroin. Parkinson Foundation's Langston, who was on the staff of the Santa Clara Valley Medical Center, where the addicts were treated, isolated the contaminant in the synthetic heroin. He discovered that the toxic contaminant destroyed the same dopamine-producing nerve cells in animals as the ones lost in patients with Parkinson's disease.

While researchers do not believe the heroin contaminant is the cause of Parkinson's in older Americans, they suspect that related chemicals may be involved. Candidates include chemicals found in some pesticides and herbicides. Several studies suggest that living in rural areas, where the use of pesticides and herbicides is widespread, may increase a person's risk of developing Parkinson's.