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Pig Tissue May Aid Parkinson’s Treatment : Medicine: Results in rats are encouraging, report says. Proponents say new procedure would bypass ethical and accessibility problems of using human fetal cells.

TIMES MEDICAL WRITER

U.S. physicians are poised to begin a new era in the surgical treatment of Parkinson’s disease, one that proponents say will bypass the ethical and accessibility problems of using human fetal tissue transplants and be safer than the now widely used pallidotomies, in which a small part of the brain is destroyed.

The new approach involves implanting fetal pig brain cells, which are readily available and remarkably similar to human tissues.

A team from Harvard Medical School reports today in the journal Nature Medicine that the fetal pig cells, when transplanted into rats, can accurately rewire damaged portions of the brain, alleviating Parkinson-like symptoms in the rats.

Based on these and other findings, a team from the Lahey Hitchcock Medical Center in Burlington, Mass., has successfully transplanted fetal pig cells into four human patients with results that so far appear to be encouraging. Early next year, the group plans to begin using the cells in Huntington’s disease patients.

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Researchers from at least three other medical centers who have been transplanting human fetal cells are also close to switching over to the new source of tissue.

Although only four patients have been treated so far, many researchers believe that on the strength of the animal results, the technique may represent a revolution in the treatment of Parkinson’s disease, which affects 500,000 to 1 million Americans, most of them over age 55. Moreover, the fact that the approach has been found safe so far in humans suggests that much larger numbers could follow as scientists search for an alternative to scarce and controversial fetal tissues, researchers said.

“If this is effective, it will be a wonderful development,” said Dr. Curt Freed of the University of Colorado.

“I’m very excited about the concept,” said Dr. C. Warren Olanow of the Mt. Sinai School of Medicine in New York City. “With human fetal tissue cells,” he said, “we’re getting consistent clinical improvement. . . . If we could get a more reproducible, reliable, consistent source of tissue, this could be a very good treatment and one that is certainly worth pursuing.”

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The first person to receive the fetal pig cells was Tony Johnson, a 57-year-old civil engineer from Taunton, Mass. who has endured Parkinson’s for 27 years. In April, Dr. James Schumacher of the Lahey clinic implanted a quarter-milliliter of cells--"a little drop on your fingertip"--from five fetal pigs into one side of Johnson’s brain.

Schumacher said it is too early to tell whether the cells are working, but Johnson’s wife, Mildred, recently told the Boston Globe that “his speech is much better, he can walk better, and he’s definitely turning around. You can see signs the cells are definitely starting to work. . . . It’s almost like a miracle.”

The disorder, whose cause is unknown, is characterized by tremors and rigidity in the limbs and loss of muscle control. As many as a third of the patients also develop dementia, an impairment of thought processes.

Parkinson’s results from the death of brain cells that produce a neurotransmitter called dopamine, which plays a key role in transmitting commands from the muscle control centers. The disorder is treated with a drug called L-dopa, which alleviates symptoms by producing dopamine in the brain. But many patients do not respond to L-dopa, and most who do eventually become resistant to its effects.

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The first surgical attempts to treat the disorder involved implanting the patient’s adrenal gland tissue, which also secretes dopamine, into the brain. The procedure provided benefit to some patients, but results were inconsistent.

Most researchers have thus shifted to human fetal brain tissues. These cells not only produce dopamine but they also secrete growth factors and have other functions as well. “Fetal cells do a lot of different things,” said Dr. Deane B. (Skip) Jacques of the Hospital of the Good Samaritan in Los Angeles. “That’s why they work so well.”

“They are not a cure for Parkinson’s disease, nor do I think they will ever cure Parkinson’s disease, but fetal tissue transplants clearly are useful,” said Dr. Abraham Lieberman of the Barrow Neurological Institute in Phoenix and clinical director of the National Parkinson Foundation.

But fetal tissue is already scarce. Good Samaritan can do only two procedures per month because of the difficulties of obtaining and safety testing fetal tissue, and doctors never know how much they will have when an operation is scheduled, Jacques said. The situation will undoubtedly become worse as new drugs, such as methotrexate and RU486, change the way abortions are performed and reduce the availability of fetal tissue.

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“Then, what are we going to do?” Jacques asked.

The answer, he said, may lie with fetal pig tissue.

“The value of porcine [pig] tissue is that it is available,” Lieberman said. “It’s a reliable source.”

The Harvard team has tested the cells in rats and primates and found that they work just as well as human cells. Other researchers, including Jacques, have obtained similar results. “Implanting pig cells in rats is just as effective as implanting rat cells,” Jacques said.

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And the cells are clearly doing more than just releasing dopamine. Today’s Nature Medicine report shows that the cells not only survive in rat brains, but that they send out axons and make the proper connections, called synapses, to other brain cells to become integrated into the brain.

“We’re fairly convinced that there is sufficient evidence to say the mechanism by which they recover is through new synaptic connections,” Isacson said. That is particularly important, he noted, in attempting to treat Huntington’s disease, where there is not a neurotransmitter lacking.

Pigs were selected, said Harvard neuroscientist Dr. Ole Isacson, who headed the project, because their organs are the closest to humans. Pig heart valves are being used in humans and researchers are experimenting with transplantation of genetically modified pig organs, such as hearts--although none of those have made it into humans yet.

“Pig nerve cells can perform all the normal functions of a human nerve cell,” Isacson said. “And we are only replacing about one-billionth of the cells in a brain, so there is no risk of acquiring pig characteristics.”

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Pig brain cells are virtually identical to human brain cells. Humans just have a much larger number of them.

And because the brain is what scientists call an “immunologically privileged” site, less likely to reject a foreign organ, surgeons do not have to use as large a dose of immunosuppressive drugs as they would with a pig heart, said neuroscientist Jonathon Dinsmore of Diacrin, the Charlestown, Mass., company that provides the cells.

Pigs used in the process are raised on a farm just like pigs used for food. Those selected are screened for viruses and disease, then placed into a “barrier facility” where they are protected from further infection until their fetuses are harvested.


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