Brain Graft Brings Surprising Gains for Parkinson’s Patients
Only a year ago, Joseluis Meza could not speak clearly, walk, dress, bathe or feed himself without help. Today, the 34-year-old victim of Parkinson’s disease can do all that and more, including kick a soccer ball with his 5-year-old son, Mario.
Meza is the beneficiary of an experimental surgery performed 10 months ago by a little-known neurosurgeon here that has taken the world’s brain researchers by surprise.
Some of them have examined Meza and other patients of Dr. Ignacio Navarro Madroza at the government-operated hospital, Centro Medico La Raza, and have come away impressed. Others are eagerly awaiting the forthcoming publication of Madroza’s data in the prestigious New England Journal of Medicine.
Many researchers agree that if Madroza’s unprecedented results can be duplicated elsewhere, it will offer new hope to millions of Parkinson’s patients and perhaps victims of other degenerative brain diseases.
Similar Results
More recently, Madroza has performed the same surgery on seven other Parkinson’s victims, achieving nearly the same dramatic results.
The operation involves transplanting tissues from a patient’s adrenal glands--walnut-sized organs located near the kidney--into the brain. The adrenal cells secrete a brain hormone, dopamine, that is involved in the control of muscular activity. Parkinson’s patients are deficient in dopamine.
This approach had been tried on four other humans, in Sweden; the recipients showed much less improvement, and those improvements disappeared within two months.
What Madroza has done differently is to implant the adrenal tissues at a different location in the brain.
“The results are in line with what we have seen,” said Lars Olson of the Karolinska Institutet, where the earlier transplants were performed in the last four years. “But the effects are better and more long-lasting.”
Madroza discussed his results at a meeting of the Society for Neurosciences in Washington last month. One scientist who heard that talk was neurobiologist William J. Freed of the National Institute of Mental Health. “What he has done makes a whole lot of sense,” Freed said. “I am very optimistic about the whole thing.”
Others who heard the talk, however, were more apprehensive because the results were being reported by a group of scientists who had previously published few papers on brain grafting in animals and who are clearly outside the mainstream of the scientific establishment that has been experimenting with brain grafts.
“There is some skepticism about his results, simply because they are so unexpected,” said neurobiologist Curt Freed of the University of Colorado Medical Center. “But I must say, everybody was struck by them.”
“If it had come from a group with a history of solid achievements in animals, I would accept it without question, knowing the history of the team,” added neurobiologist John R. Sladek Jr. of the University of Rochester. “But I don’t know that team, so it is very difficult to accept (the results).”
The cause of Parkinson’s disease is unknown. Its symptoms include tremors and rigidity of the limbs. About 30% of Parkinson’s victims also suffer dementia, an impairment of mental function.
Parkinson’s can be controlled, at least in its early stages, by use of the drug L-dopa, which increases the brain’s dopamine supply. As the disease becomes more severe, however, patients receive less benefit from the drug.
Starting in the 1970s, scientists such as Sladek, Bakay and both Freeds began laying the groundwork for human experiments by showing that Parkinson’s-like symptoms in animals can be ameliorated by grafting adrenal cells, fetal brain cells, or adult brain cells from other animals into the brains of the afflicted animals.
Symptoms Reversed
William Freed, for example, has reversed Parkinson’s symptoms in primates by implanting the specific adrenal cells that secrete dopamine into the animals’ lateral ventricles--fluid-filled cavities on both sides of the caudate, the central part of the brain that controls bodily functions.
Then in Sweden, Olson’s team used a similar technique on humans, with a slight twist. Hoping to amplify the effects of the grafted cells, they injected the cells deep inside the caudate itself so that the secreted dopamine could more easily reach the cells that require it. But this approach was not entirely successful.
“Either we have transplanted too few cells to give any permanent (beneficial) effect, or too many (of the cells) have died” from lack of nutrients, Olson said in a telephone interview from Stockholm. Most other investigators believe that the cells died.
More Conservative
In contrast, Madroza and his colleague, neurobiologist Rene Drucker-colin of the University of Mexico, have adopted the more conservative approach of mimicking the animal experiments.
“We nick the surface of the caudate surgically and implant the adrenal medullary cells in this bed so that they are half in the caudate and half in the ventricle,” Drucker-colin said.
In this manner, the cells receive nutrients from the fluid in the ventricle, but they are still in intimate contact with the caudate so that the dopamine reaches the cells.
This approach has apparently increased cell survival. One of Madroza’s patients died from unrelated causes about a month after the grafting operation. “An autopsy showed that capillaries were growing into the grafted tissue and providing nutrients,” Madroza, 43, said. “Very few cells were dead.”
Younger Patients
Of the seven other patients on whom Madroza has performed the surgery, including Meza, three were under 50 years old. While 95% of Parkinson’s patients are over 50, Madroza said he chose some younger patients because he thought the surgery would be more effective for them. Experiments in animals have shown that adrenal glands from young animals are much more effective in reversing Parkinson’s symptoms than those from older animals.
“All of the seven have improved,” he said in an interview here. “But the greatest improvement was in the younger patients.” The younger patients have lost 80% to 90% of their tremor and as much as 80% of their rigidity, Madroza said. The older patients lost about 60% to 80% of their tremor and as much as 60% of their rigidity.
Two of the older patients also suffered from dementia, but the transplant did not affect it.
Hormone Injections
Despite Madroza’s success, the Swedes do not yet intend to change the location of where they have been injecting the adrenal cells. Instead, they are working in animals to develop ways to continuously inject into the brain a hormone called nerve growth factor, which might enhance the survival of the transplanted adrenal cells.
Most experts contacted by The Times last week were very cautious in assessing Madroza’s results. “I’d like to see a lot more data about what the patient’s condition was before and after the surgery,” said neurobiologist Don Stein of Clark University.
Researchers like Stein say there are two potential problems with Madroza’s approach, and only time will tell if they are serious obstacles.
Many fear that the beneficial effects may actually arise from damage associated with the surgical procedure itself, rather than from the transplanted tissue. “More than 30 years ago, Irving Cooper developed a technique to relieve symptoms (of Parkinson’s) by damaging a small part of the brain,” according to neurologist Irwin J. Kopin of the National Institutes of Health.
But that procedure was never widely used and has been abandoned because the results were inconsistent and the effects were transient. Kopin conceded that Meza’s improvement has persisted much longer than that in any of Cooper’s patients.
Difficult Process
A second potential problem is the difficulty in separating adrenal medullary cells, which secrete dopamine, from adrenal cortical cells, which secrete steroid hormones. Some observers fear that any cortical cells left in the grafted tissue could proliferate and form a benign tumor in the brain.
This is also a potential problem with the Swedish approach, but so far there has been no sign that the cortical cells are proliferating in any of the 11 surviving transplant patients.
Madroza’s work has been widely reported in the Spanish press, and he is rapidly becoming something of a national hero in Mexico. And here, much has been made of the fact that Madroza, unlike most prominent Mexican scientists who studied in the United States, received all his training in Mexico.
He received both his M.D. and Ph.D. in neurosurgery from the University of Mexico.
Madroza now is seeking permission from his hospital’s ethics committee to perform five more transplants.
Eventually, he also hopes to implant fetal brain cells or cells grown in culture. Such an approach, he said, would provide a better source of tissue and will do away with the trauma of removing the adrenal gland.
Meza, meanwhile, is undergoing extensive rehabilitation to improve the strength of his muscles. He is working very hard to improve his writing ability, he said, and he hopes to regain his job keeping track of trains for the National Railroad.
Until then, he strolls through his neighborhood and helps his wife in her small business selling fruits, vegetables and pigs. He also spends a great deal of time with Mario and his 6-year-old daughter, Claudia.
Meza said he believes he will continue to improve because “I feel better everyday.”
