Drug Is Found to Delay Progression of Parkinson’s
Scientists have demonstrated for the first time that a drug treatment can delay the brain-destroying progression of Parkinson’s disease.
In a California trial involving 54 patients, the drug, called deprenyl, nearly doubled the time that elapsed between the onset of Parkinson’s and the need for therapy with the most commonly used drug, L-dopa, researchers from the California Parkinson’s Foundation in San Jose report in today’s issue of the journal Science.
L-dopa does not slow the normally fatal disease, which usually strikes people over the age of 50, but it does alleviate its symptoms, which include disabling tremors and rigidity of the limbs and, in at least 30% of the cases, mental impairment.
Combined with earlier anecdotal reports suggesting that deprenyl prolongs the lives of Parkinson’s victims, the research suggests that powerful relief will soon be available for Parkinson’s victims, who number over 1 million in the United States alone. Deprenyl is scheduled to be marketed as a prescription drug next month.
But the discovery has implications even beyond that. Two other conditions associated with aging, Alzheimer’s disease and amyotrophic lateral sclerosis (Lou Gehrig’s disease), also involve inexorable degeneration of brain cells, and physicians have not been able to slow their progression either.
The fact that disease progression has been slowed in Parkinson’s “raises the hope that you can do it with the others as well,” said neurologist J. William Langston, the principal investigator of the new study.
The new results are “very important,” said neurologist Stanley Fahn of the Columbia University College of Physicians and Surgeons, co-chairman of a larger study of deprenyl--called DATATOP--that is now under way at 28 clinical centers throughout the country.
Langston’s study served as a pilot program for DATATOP. Results from the larger study are not expected until late 1990 at the earliest, and Fahn refused to comment on them. But rumors circulating in the neurological community suggest that those results will support Langston’s findings.
And Langston’s results could have an immediate impact on treatment of Parkinson’s in this country. Six weeks ago, the U.S. Food and Drug Administration approved marketing of deprenyl for use in combination with L-dopa for treating patients late in the course of Parkinson’s. Somerset Pharmaceuticals of Denville, N.J., will begin marketing the drug as Eldepryl in mid-September, and once they do, physicians--as they may with any drug--will be free to prescribe it for any use they see fit.
Fahn noted that it is “inevitable” that large numbers of neurologists will “jump on it (deprenyl)” for their patients in the early stages of the disease.
Parkinson’s disease results from the death of cells in the substantia nigra portion of the brain that secrete the neural transmitter dopamine, which plays a key role in the control of muscle movement. The disease’s cause is unknown, but growing numbers of neurologists believe that it is produced by chemicals in the environment that poison the dopamine-secreting cells.
As production of dopamine is slowed, the victims lose control of their limbs until they eventually become completely disabled. L-dopa is used in therapy because it is converted into dopamine in the brain, increasing the brain’s dopamine supply. But it is effective, on average, for only about six years, after which symptoms worsen.
Some researchers have attempted to cure Parkinson’s by transplanting dopamine-secreting cells from the adrenal glands or from fetuses into the brains of victims. But those procedures have been attempted on only about 300 patients and there is still no consensus on their value.
In contrast, deprenyl could be used with virtually every Parkinson’s patient.
For their study, Langston and neurologist James W. Tetrud recruited 54 patients who had recently been found to have Parkinson’s disease. Half were given twice-daily doses of deprenyl and half were given a placebo--a sugar pill with no effect. The patients were monitored until either they had been in the study for three years or their condition became severe enough to require L-dopa.
They found that the average time before L-dopa was required was 312 days in the placebo group and 549 days in the deprenyl group.
Langston and Tetrud also rated the patients’ neurological condition on five separate scales. They found that, based on these scales, disease progression was slowed by 40% to 83% per year.
“The clinical observations suggest that the disease is progressing more slowly . . . and that’s compelling evidence, but it is not proof,” Langston said in an interview. “To prove it, we would have to demonstrate that nerve cells are surviving over time, (a procedure) that is not currently possible in living humans.”
At the end of the study, the patients were taken off deprenyl for a month to ensure that the apparent slowdown in disease progression was due to the preservation of nerve cells and not simply to relief of symptoms. The drug therapy was then restarted and the researchers will continue to monitor the patients to determine whether the drug continues its effects for longer periods.
Ironically, deprenyl has been used in Europe for about 15 years to treat patients who have begun to develop tolerance for the effects of L-dopa. In one key study, pharmacologist Moussa B.H. Youdim of the Technion-Israel Institute of Technology found that combined use of L-dopa and deprenyl substantially increased the survival of Parkinson’s victims.
But that study was viewed with “a great deal of skepticism,” according to UCLA neurologist Charles H. Markham, because it was an uncontrolled study on an unusual group of Parkinson’s patients. Langston’s results, however, would seem to provide strong support for Youdim’s conclusions.
The $10-million DATATOP study has a design similar to Langston and Tetrud’s but involves 800 patients. Some of those patients are also receiving Vitamin E as well as deprenyl, however, to determine whether Vitamin E can also slow the disease, as animal experiments have suggested.
If the DATATOP results confirm Langston and Tetrud’s, Fahn said, researchers will almost certainly begin studying the long-term combined effects of L-dopa and deprenyl to determine if people will in fact live longer.
PARKINSON’S DRUG
Parkinson’s disease is caused by the death of cells in the substantia nigra at the base of the brain that release a hormone necessary for controlling muscle movements. Mounting evidence indicates that metabolites of environmental chemicals, such as pesticides, can kill the cells, causing the disease. The drug deprenyl delays the progression of Parkinson’s by blocking conversion of the chemicals into their toxic form.
