Back To Normal

By Claudia Wallis

The symptoms had begun in their early 30s for both men. First there was the mild stiffening of limbs and the tremors that mark the onset of Parkinson's disease. Then came the gradual loss of muscle control, leaving them prisoners in their own bodies -- mentally lucid but physically unable to eat, urinate or comb their hair without assistance. Levodopa, the most common treatment for the debilitating illness, had ceased to work for one man and could not be tolerated by the other. Nor were other drugs of use. Facing further deterioration, the two agreed to become guinea pigs in a remarkable experiment conducted at La Raza Medical Center in Mexico City and reported in last week's New England Journal of Medicine. The results: one man, previously confined to a wheelchair, can now play soccer with his son and hopes to return to work; the other is no longer incapacitated by incessant trembling and can speak clearly for the first time in years.

The procedure that brought about these transformations is an unusual transplant operation, in which tissue taken from one of the adrenal glands, located above the kidneys, is implanted into the brain. Doctors have known for years that the symptoms of parkinsonism result primarily from the death of cells in a darkly pigmented part of the brain known as the substantia nigra. This region serves as a production center for dopamine, a vital neurotransmitter that helps govern such voluntary actions as walking and speaking. As it happens, there is another site in the body, outside the brain, that produces substantial amounts of dopamine: the inner core of the adrenal glands. By transferring dopamine-producing adrenal cells into the brain, Dr. Ignacio Madrazo and his colleagues hoped to replenish the supply of this neurotransmitter and thus restore normal function.

To Madrazo's amazement, the effects of the operations, performed in March and October of last year, became apparent in a matter of days. In the case of one of the two patients, he noted in the Journal, "functional recovery occurred on an almost daily basis." Both men are now leading normal lives, says Madrazo, and one has resumed managing his own farm. The loss of one adrenal gland has not presented any complications. Nor is rejection a problem, because the grafted tissue is the patient's own. Encouraged, Madrazo's team has tried the procedure on eight other patients. They are "doing well," Madrazo says, but it is too soon to assess the effects.

The transplant procedure was not without precedent. Beginning five years ago, doctors in Sweden tried similar surgery on four Parkinson's victims. They achieved only slight improvements that soon faded. Madrazo credits his team's success to modifications in surgical technique. The Swedes had transferred the adrenal tissue directly into a C-shaped structure in the middle of the brain called the caudate nucleus, where dopamine exerts its primary effects. The Mexicans, by contrast, used surgical staples to anchor the cells onto the exterior of the caudate, which is continually bathed in cerebrospinal fluid. This nourishing bath may have helped the graft survive. In addition, Madrazo says, he transplanted "much more" tissue than did his predecessors.

For the estimated 1 million Americans with Parkinson's disease, the Mexican research offers new hope. "If these results turn out to be valid and replicable, this would be a major advance," says Neuroscientist William Freed of the National Institute of Mental Health. Current treatments for Parkinson's are far from ideal. Levodopa, which is chemically related to dopamine, can cause irregular heartbeats, paranoia and depression, and ceases to be effective after prolonged use. Freed and others are eager to see if the new technique will work in older patients (most Parkinson's victims are over 50), and if its benefits will last. If so, says Freed, "the procedure could eventually have implications for treating other neurological disorders, such as Alzheimer's and Huntington's diseases."

With reporting by Andrea Dabrowski/Mexico City and Andrea Dorfman/New York