Specialists see pope's illness worsening
Researchers strive to treat Parkinson's
For more than a decade, Pope John Paul II has suffered through Parkinson's disease in the international spotlight, his hands trembling, his once-stout posture slumped, his sermons slurred, as the neurological disorder slowly entraps his body. Now, as he celebrates 25 years as pontiff in Rome this week, concerns are intensifying that the disease may soon kill him.
Two close papal associates warned publicly in recent weeks that the pope's days may be nearing an end. Last Tuesday, the pope requested, "Pray for me, today and always."
Neurology specialists say the extreme rigidity in his face indicates troubles with breathing and swallowing, which can lead to fatal infection.
Even if the pope lives for years more, his severe physical decline is likely to continue. The pontiff's ability to speak, write, walk, and stand -- in other words, to communicate with the world's Catholics -- will become more limited by the year. Dementia also looms.
But the pope's very public deterioration occurs as researchers are increasingly hopeful about treatment for the millions of people who suffer from Parkinson's disease, which kills off brain cells that control bodily movement. Although the breakthroughs will probably come too late for John Paul II, researchers say the coming decade seems filled with promise for patients.
New brain implants deliver tiny shocks that dramatically reduce symptoms, even when standard drug therapy fails. Studies show that caffeine offers protection against the disease, pointing the way to potential new drugs. Research using stem cells harvested from human embryos, work that the pope opposes, may soon be able to provide replacement brain cells to treat the disease. And genetic research has led to early clinical trials of drugs designed to prevent Parkinson's disease similar to the way anticholesterol pills stave off heart disease.
"There are definitely going to be better ways to manage the disease," said Dr. Bradley T. Hyman, a researcher at the neurogenerative disease institute at Massachusetts General Hospital, which is active in research on Parkinson's. "But what we prefer is preventing the disease in the first place . . . We're working on heroic interventions."
The disease is something of a mystery. Although 1 million Americans suffer from Parkinson's, doctors know little about what triggers it or how it destroys the brain cells crucial for bodily movement.
The 83-year-old pontiff, a major player on the world stage over the last quarter-century, is now a typical late-stage Parkinson's disease patient, unable to move about in the most basic ways.
There is no clear provision in Catholic law to remove a pope. He can step aside, although John Paul has said he will serve until death, a pledge that inspires some Catholics but frustrates many others.
"Are we, in fact, in a lame duck situation?" said Thomas Groome, a theologian at Boston College. "There is the impression that critical issues have been put on hold for this pontificate." Groome said crises over war, clergy sex abuse and homosexuality require a vigorous, engaged pontiff.
But specialists on Parkinson's disease predict that the pope will be anything but vigorous.
"He looks like he has typical Parkinson's disease that's advancing," said Dr. Michael Schwarzschild of MGH. "It looks like it's fairly debilitating."
The disease slowly destroys brain cells that make dopamine, a chemical messenger critical to movement. Current drug treatments, which can be effective for up to a decade, try to increase dopamine levels. But eventually too many cells die, and patients worsen, with alarming results: muscle rigidity, tremors, poor balance, stooped posture, and trouble swallowing, speaking, and breathing.
Witnessing these symptoms up close after a visit to the pope several weeks ago, Cardinal Christoph Schoenborn, the archbishop of Vienna, said John Paul II "is approaching the last days and months of his life."
Schoenborn's comments were followed by published comments from papal adviser Cardinal Joseph Ratzinger that the pontiff was "in a bad way."
Schwarzschild said he is wary of accepting cardinals' pronouncements on medicine but noted that others in the pope's condition face a very real threat of death. With elderly patients in the late stages of Parkinson's disease, like the pope, doctors constantly fear pneumonia and infection, he said. It is these afflictions, rather than the disease itself, that often kill.
Muscle rigidity and immobility can lead to falls, broken bones, and then infection. But with attendants constantly at his side, the pope is less likely to suffer such accidents than most patients, specialists said.
Instead, the degeneration of axial muscles in his head and neck, used for breathing and eating, is more of a threat. Such muscle failure can leave bacteria-filled spittle or food in throat cavities that leads to infection or pneumonia. Specialists said the pope's facial rigidity indicates he might have considerable axial muscle incapacity.
Another threat is mental decline and dementia, suffered by many late-stage patients. Vatican officials have never released details on the pope's mental health.
About 1 percent of Parkinson's patients seem to have inherited genes responsible for the disease. By studying them, scientists have zeroed in on a protein, alpha-synuclein, that invades brain cells in patients. They also noticed that cells produce so-called chaperon proteins that try to fight off alpha-synuclein but eventually lose.
The researchers at MGH are working on medications that would augment the supply of chaperon proteins, conceivably preventing the disease from emerging in at-risk patients, Hyman said. Rather than simply seeking to readjust dopamine levels, as current drugs do, this new approach tries to disrupt the chain of genetic events behind the disease before it affects patients. Clinical trials of several drugs like this, which home in on the disease at the cellular level, are underway at dozens of sites around North America, with initial results for many expected within two years.
Another treatment that some scientists say holds great promise is stem cell therapy, in which researchers convert the chameleon-like cells into replacement dopamine-producing brain cells. But the procedure involves use of human embryos, drawing criticism from the pope and others.
This month, researchers at Memorial Sloan-Kettering Cancer Center in New York reported that they used stem cells to alleviate the symptoms of Parkinson's in mice. Several similar studies are in the works elsewhere.
Of far more immediate value to patients is deep brain stimulation. Surgeons implant devices similar to a pacemaker that fire charges into the brain region affected by Parkinson's disease, balancing out the brain messages distorted by the disease.
"We've seen a pretty dramatic improvement in patients. Many patients have a significant reduction in their medications and in some cases are able to return to work," said Harvard neurosurgeon Dr. Enad Eskandar, who has operated on about 40 patients in three years. "I recently had a landscaper back to work."
Researchers also have found hope in a morning staple.
"The more coffee people consume, the less likely they are to have the disease later in life," Schwarzschild said. "That's true with tea and soft drinks as well."
Although there is no proof caffeine works, researchers have developed an experimental drug to treat Parkinson's disease, KW6002, that acts like caffeine on brain cells. Results are expected in several years.
Material from the Associated Press was used in this story. Raja Mishra can be reached at rmishra@globe.com.
