Buyer's Guide to Stem Cells

 

   

1.Politics and potential

2.Meet the stem cells

3.Troublesome treatment

4.Treating Parkinson's?

 

Washington lawyer Jeffrey Martin wants to get stem cells research moving. He sees it as a matter of life and death.
Courtesy Mary Beverly

 

 

 

 

 

photo of Michael J. Fox
Michael J. Fox

 

 

 

 

 

 

 

 

 

Death of the neurons in the substantia nigra cause Parkinson's disease
Copyright and courtesy Digital Anatomist Program, University of Washington, Seattle

   

Putting stem cells to work
With brown hair, Martin smiles at the camera.Jeffrey Martin is a man with a mission, a man in a hurry. Martin, 47, learned three years ago that he has Parkinson's disease, and wants action before he gets sicker. Before he loses the ability to move. Before Parkinson's disease kills him.

Martin's problem is simple: Maybe a million cells in his brain have died. Normally, a million cells might not cause major trouble in an organ as big as the brain, but the dead cells made dopamine, which you need to move. Eventually, Parkinson's, is fatal.

Parkinson's afflicts mainly the elderly, but also such high-profile folks as former Attorney General Janet Reno, former boxer Muhammad Ali and actor Michael J. Fox.

Martin, a Washington lawyer, is trying to work the levers of government to ensure that promising research is funded while he and the million other Parkinson's patients in the United States can benefit. And to him, stem cells are about the best bet around. "I'm convinced that if the right management and funding decisions are made by government, we have the potential within four to five years to solve -- to cure -- many forms of Parkinson's," Martin says.

He notes that during the campaign, George W. Bush advocated a 'medical moonshot,' to cure a number of age-old diseases. Parkinson's disease will be on the short list because we are so close..."

Can't move
Parkinson's starts with mild symptoms -- a mask-like face, an inability to initiate movement, and moves to generalized stiffness, tremors and immobility that eventually becomes fatal. "It's a slow-progressing neurological disorder; there's no proven way to slow it," says J. William Langston, president of the Parkinson's Institute.

Brain diagramed to show location of substantia nigra.The key problem, Langston says, is the death of dopamine-producing neurons in the substantia nigra (black stuff) deep in the brain; symptoms appear when about 80 percent of the cells die. Parkinson's has become a test case for cell transplant because the damage is so localized. Since the cells are "dead and gone," Langston says, the best cure would be cell replacement.

Such replacement has been tried in Sweden, using fetal brain cells, Ole Isacson told the 2001 meeting of the American Association for the Advancement of Science in San Francisco, and many patients improved. "Fetal cells have worked for 10 years in several patients, they are releasing dopamine," he says, adding that about 150 Parkinson's patients worldwide have gotten these transplants.

Fetal cells are tough to use, and not just for ethical and political reasons, but also because they have varying genetics and are hard to collect. A quest for other sources included a 1995 test of pig brain cells, which produced some "reasonably encouraging results" but troublesome immune rejection.

Limited success
Problems with human fetal and pig cells leave two options for transplantation: embryonic and adult human stem cells. It's not clear whether adult neural brain cells can, like fetal-derived stem cells, form dopamine-making neurons, but embryonic stem cells seem promising. Isacson recently implanted embryonic stem cells into mice. Although reluctant to speak in detail before the study is published, he would say the "Cells are behaving in the way we'd hoped; the cells appear to be very functional."

Embryonic cells, which might multiply inside the patient, would have a major advantage over fetal-derived cells, which often die, he says. "We'd get a ten-fold increase in the implants, rather than a 90 percent loss, as in a fetal-cell graft."

The body's innate "smarts" seems to help in the crucial issues of knowing where to go and what to do. Transplantation typically involves squirting cells through a tiny tube, and while it's hard to hit an exact target, that has not posed a significant problem so far. "No matter where the stem cells are placed, they seek out their normal targets," says Isacson. "The brain circuitry is very tightly controlled."

Summing the cell
Ronald McKay, a long-time stem cells researcher at the National Institutes of Health, is also positive about spare-parts therapy for neurological diseases. He told a recent seminar at the American Association for the Advancement of Science, "Embryonic stem cells generate [dopamine-making] neurons that look really good." If you're trying to cure Parkinson's, he says, "There's no other source of such a large number of cells."

The view from the Parkinson's sector is almost, but not quite, as positive. Langston, who has worked on the disease for more than a decade, observes that drug treatment, using a chemical the body can convert into dopamine, typically works for a year or more. When it fails, the patient may turn rigid again, or suffer excessive motion or even psychosis.

Langston notes that while fetal-cell transplants showed promise, they sometimes worked too well. "Several patients got dyskinesia [excessive, uncontrolled motion], as if the graft became uncontrolled." The dyskinesias was even worse than those sparked by drug treatment, he adds.

Still, he says, there is no good treatment for Parkinson's now, and replacing the body's equipment seems more hopeful than finding better drugs. "Stem cells are the most promising long-term treatment or cure."

Here's our stem-cell bibliography.

 

   

 

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