L-Dopa for Parkinson's

In the vast majority of cases of Parkinson's disease, or "shaking palsy," physicians cannot be sure what originally caused the nerve damage that results in the patient's tremor, muscle rigidity, forward-falling posture, hasty gait and "pill-rolling" movements of the fingers. As with most diseases of which the basic causes are unknown, there is a yard-long list of drugs that have been tried; some give modest relief, but all fall far short of cure. Even radical brain surgery usually relieves only some of the symptoms. Now a new drug has been found that is more effective in most cases than earlier medicines and promises real progress in future Parkinsonism treatment, once it is thoroughly tested. Unfortunately, it has already touched off a flurry of premature hope among U.S. Parkinsonism victims, variously estimated at between 300,000 and 1,500,000.

The drug is L-dopa, short for Levo-dihydroxyphenylalanine. The rationale for its use lies in the fact that the brains of Parkinsonism victims are deficient in dopamine, a natural body chemical essential to normal nerve activity in the midbrain. So, researchers reasoned, why not give the patients extra dopamine? The trouble is that dopamine cannot cross the natural barrier be tween the bloodstream and the brain to reach the deprived cells. But dopa, an amino acid that comes in three forms including L-dopa, crosses the barrier by a process not yet fully understood. It is broken down in the brain to yield the desired dopamine.

Tailored Doses. In the small hospital that is part of the Atomic Energy Commission's Brookhaven National Laboratory on Long Island, Dr. George C. Cotzias tried an early, less purified form of dopa and obtained confusing results. Some patients with mild early symptoms got no better; others with more severe disease improved markedly, but in some cases the side effects, such as vomiting, were intolerably severe. Cotzias forecast that the more refined L-dopa form of the drug might be better, and manufacturers began to produce it in increasing amounts.*

Now Cotzias has reported results for 28 patients treated with L-dopa for as long as two years. In earlier trials, the drug had been given intravenously and in small doses. Cotzias gave it by mouth and built up the dosage steadily to much higher levels. Because L-dopa may decrease appetite drastically and upset the metabolic system, patients must be studied closely in a metabolic ward. Dosage must be individually tailored, even to fixing the best times of the day for each patient to take his capsules. The buildup to maximum doses takes five to seven weeks. Patients must be watched closely for possibly dangerous blood-pressure changes, disorders of the white-blood-cell system and abnormal, involuntary muscle movements, such as gesticulating and grimacing.

Taking all these precautions, Cotzias found at least partial improvement of some symptoms in every case, including some that were crippling in severity and had been neglected for years. The most dramatic improvement was displayed by patients with moderately severe disease. First they regained the ability to make voluntary movements, next their rigidity was relieved, and finally tremor decreased. Inability to speak, poor articulation, excessive sweating, weeping and urinary disorders were "strikingly improved," as were mental attitudes. Some patients who had been apathetic and vague showed an "awakening intellect" with better memory and alertness. Several who had not been able to get out of a wheelchair unaided or to walk without fall ing can now do both.

Even modest improvement in severe cases may be lifesaving, Cotzias points out. One patient who for years had been unable to walk or talk, and hardly able to swallow, recovered sufficiently to walk with assistance, to feed himself, and occasionally to speak. This improvement lasted during the year that he spent at Brookhaven. He died in another hospital, from pneumonia caused by getting food in his lungs, after he had been without L-dopa for some time.

Electronic Breaks. So far, only a few medical centers in the U.S. are test ing L-dopa, which can be used only by research physicians, since it has not been approved by the Food and Drug Administration for general prescription. Results at Manhattan's Neurological Institute over a six-month period and at Miami's National Parkinson Institute are similar to Dr. Cotzias'. The National Institutes of Health and the Parkinson's Disease Foundation are work ing to increase the number of centers that will be approved for L-dopa trials.

Cotzias has his eye on a more remote and desirable goal than the treatment of a single disease, even such a common crippler as Parkinson's. He holds with Chemist Linus Pauling (TIME, May 3) that biochemical deficiencies in the brain may masquerade as brain-tissue degeneration. The deficiencies may result from underlying damage to neurons (the electric regulators of the nervous system) or other causes, but either way they produce "electronic breaks," so that nerve impulses do not get through. Dr. Cotzias wants to find more ways of repairing more kinds of electronic breaks.

* The drug is not patentable, and the substance occurs naturally in broad beans and velvet beans. A well-equipped chemical factory can easily extract it.

This file is automatically generated by a robot program, so reader's discretion is required.