Mexican Technique Inspired U.S. Brain Graft Team
Surgeons at Vanderbilt University here rushed ahead with a pioneering brain graft surgery within two weeks of publication of an article in the New England Journal of Medicine suggesting that the technique developed by Mexican researchers could reverse the effects of Parkinson’s disease.
“It is important that somebody confirm (the Mexican) results as soon as possible,” neurosurgeon George S. Allen, leader of the Vanderbilt team, said Friday.
In a five-hour operation Thursday morning, surgeons John L. Sawyers and John R. Potts removed one of Dickye Bagget’s two adrenal glands from its normal position above the kidney and minced the tissues. Guided by a computer, Allen and neurosurgeon Noel E. Tulipan then used a long, thin needle to implant them in the brain of the 42-year-old housewife.
They hope that the implanted cells will secrete chemicals that will reverse the course of Bagget’s disease, which is generally characterized by severe tremors and rigidity of the limbs.
Results Not Revealed
It was the first such operation in the United States but at least the 16th in the world. Neurosurgeons in Sweden have operated unsuccessfully on four patients, and Mexican neurosurgeons have operated on 11. Chinese scientists in Beijing have reportedly also attempted the operation, but they have not published their results.
Bagget was awake within an hour after the operation and conversing with her family, Allen said. She was taken out of intensive-care late Friday, and her condition was described as fair. The physicians said they could detect no ill effects from the surgery, but Allen cautioned that it will be several weeks before the team will know whether the operation was successful.
Vanderbilt team members had been studying brain transplants in rodents and other small animals since 1982, Allen said in an interview, and had contemplated performing the surgery in humans. They already had several potential candidates for the operation in mind when the journal article appeared.
‘Major Impetus’
“The Mexican report was a major impetus for us to go ahead right away,” Allen said.
The team applied to Vanderbilt’s committee for the protection of human subjects and received approval to go ahead. The surgeons have also received tentative permission to perform the operation on as many as 17 additional subjects within the next three to four months. No permission is required from federal health agencies.
Other scientists reacted very cautiously Friday to the Vanderbilt announcement. Neurobiologist William J. Freed of the National Institute of Mental Health, for example, said he was “a little bit alarmed” that Allen’s group had proceeded with the surgery so rapidly.
Neurobiologist Don Marshall Gash of the University of Rochester School of Medicine also cautioned the investigators to proceed slowly.
“I would urge that we wait until the scientific community has the opportunity to examine the previous studies more carefully before extensive trials are carried out in the United States,” Gash said.
“The fact that it has been done in the United States doesn’t change the basic issues,” added neurobiologist Don Stein of Clark University in Worcester, Mass. “There is a lot . . . we don’t know yet about the potential bad side effects of the operation.”
Neurobiologist John R. Sladek Jr. of the University of Rochester noted, however, that “many investigators would like to see the Mexican results replicated, and I am encouraged that a group as respected as (Allen’s) has decided to do this experiment.”
Dramatic Improvement
The results that triggered the Vanderbilt team’s activity were reported on April 2 by neurosurgeon Ignacio Navarro Madrazo of Centro Medico La Raza in Mexico City and neurobiologist Rene Drucker-Colin of the University of Mexico. In their article in the New England Journal of Medicine, they reported dramatic improvement in the health of the first two patients to receive the surgery.
The first, 34-year-old Joseluis Meza, had been completely disabled before his surgery. Ten months later, when the report was written, he could speak clearly, walk and dress, bathe and feed himself. In a December interview, Meza said that his health was still improving and that he hoped to return to work soon.
The second patient, an unidentified 39-year-old man, showed similarly dramatic improvement. When the paper was written, he had had his transplant for four months.
Madrazo has subsequently performed the operation on nine other patients. Eight of them have shown improvement, although not as dramatic as that of the first two patients. One died of unrelated causes a month after surgery.
Sharp Contrast
In sharp contrast, Swedish investigators at the Karolinska Institutet in Stockholm have performed the procedure on four Parkinson’s patients. They observed only modest improvements, which disappeared within two months.
The difference between the two procedures is the site where the adrenal cells were implanted. The Swedish investigators embedded the cells deep within the brain, where they were not exposed to nutrients. Most researchers now believe that the cells died fairly quickly in the Swedish operations.
Madrazo however, implanted the cells in a naturally occurring cavity within the brain where they would be bathed in nutrients. Evidence suggests that the cells are thriving at that site, Madrazo said.
Initial reports from Nashville Thursday suggested that the Vanderbilt scientists followed the Swedish procedure. But, in fact, they followed Madrazo’s procedure almost exactly. They deviated from his work only by implanting a thin tube leading from the interior of the brain to a small reservoir implanted under Bagget’s scalp.
Withdraw Fluids
The tube and reservoir will allow the scientists to withdraw fluids from the side of the brain opposite where the cells were implanted. They hope that analysis of this fluid will enable them to determine precisely how the grafted cells are producing their effects and how a graft on one side of the brain can affect the whole brain, as Madrazo observed.
“If it works, we want to find out how it works,” Allen said.
The facts that the Mexican patients improved slowly over a long period of time and that their whole brain was affected, Allen said, “indicate that factors in addition to dopamine are having an effect.”
Parkinson’s disease is caused by the loss of brain cells that produce dopamine, which allows nerve cells to transmit messages to one another. Cells from the adrenal glands were used in the transplant because they also produce dopamine.
Bagget is not a typical Parkinson’s patient. Most of the estimated 1.5 million U.S. victims are over the age of 50 when they contract the disease. Bagget developed her first symptoms 10 years ago when she was 32, and the disease was diagnosed five years ago.
Ironically, her grandmother developed Parkinson’s disease only two years ago.
Neurologist R. Stanley Burns of Vanderbilt has been monitoring Bagget’s condition closely for the past year. She was chosen to be their first subject, he said, because “her disease has shown progression for the past year, but she is still young and in (otherwise) good health. . . .”
‘Most to Gain’
“She has the most to gain from the surgery because her disease is not as severe as many others,” he said.
Bagget’s husband, Henry, told a press conference that the prospect of the operation was “frightening, in a way” but that they went ahead with it because “we hoped it would help her and, if it didn’t, we hoped others would learn from it.”
The 45-year-old Allen said that future patients will represent a broad cross-section of Parkinson’s victims. A third of them will be young (below age 50) and moderately impaired, a third will be young and severely impaired and a third will be older (50 to 75) and severely impaired.
“We think that by studying such a cross-section we will be able to obtain a better idea of who will get the most benefits from the surgery,” he said.
Allen strongly defended the team’s decision to study a large number of patients.
“We would be unwilling to do just one or two patients,” he said, “because we don’t think we would learn very much that way.”
